bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrity assay for messenger RNA in mouse and human brain samples and synaptosomal preparations
Authors: Bujanauskiene Daina , Merkevicius Kajus , Kuliesiute Ugne , Denkovskij Jaroslav , Kutanovas Simonas , Luksys Gediminas , Rocka Saulius , Bernotiene Eiva , Neniskyte Urtė 
Published: January 2024

AbstractTraditionally, RNA integrity evaluation is based on ribosomal RNAs (rRNAs). Nevertheless, gene expression studies are usually focused on protein coding messenger RNAs (mRNAs). As rRNA and mRNA have significant structural and functional differences, the assumption that rRNA integrity properly represents mRNA integrity may not be accurate. Moreover, contrary to whole tissue RNA samples, subcellular preparations such as synaptosomes contain almost no rRNA, thus prohibiting the use of traditional rRNA-based methods to assess sample RNA integrity. Here we present a RT-qPCR based assay, which estimates mRNA integrity by comparing the abundance of 3’ and 5’ mRNA fragments in a long constitutively expressed mouse or humanPGK1mRNA. The assay was tested and validated using plasmids with cloned 3’- and 5’-ends of thePGK1cDNA reflecting different ratios of 3’ and 5’ cDNA amplicons in partially degraded RNA samples. The accuracy of integrity score calculation was ensured by integrating a mathematical correction of qPCR results to account for the variable amplification efficiency of different primer pairs. The 5’:3’ assay was used to quantify RNA degradation in heat-degraded mouse and human brain tissue RNA as well as in clinical human brain RNA samples. Importantly, the expression of housekeeping genes correlated better with 5’:3’ integrity value than with the RIN. Finally, we were even able to use 5′:3′ assay to assess mRNA integrity in mouse synaptosomal preparations that lack rRNAs. We concluded that the 5’:3’ assay can be used as a reliable and sensitive method to evaluate mRNA integrity in mouse and human brain tissue and subcellular preparations.
Competitive fungal commensalism mitigates candidiasis pathology
Authors: Kralova Jarmila Sekeresova , Donic Catalina , Dassa Bareket , Livyatan Ilana , Jansen Paul Mathias , Ben-Dor Shifra , Fidel Lena , Trzebanski Sébastien , Narunsky-Haziza Lian , Asraf Omer , Brenner Ori , Dafni Hagit , Jona Ghil , Boura-Halfon Sigalit , Stettner Noa , Segal Eran , Brunke Sascha , Pilpel Yitzhak , Straussman Ravid , Zeevi David , Bacher Petra , Hube Bernhard , Shlezinger Neta , Jung Steffen 
Published: January 2024

AbstractThe mycobiota are a critical part of the gut microbiome, but host-fungal interactions and specific functional contributions of commensal fungi to host fitness remain incompletely understood. Here we report the identification of a new fungal commensal,Kazachstania heterogenicavar.weizmannii,isolated from murine intestines.K. weizmanniiexposure preventedCandida albicanscolonization and significantly reduced the commensalC. albicansburden in colonized animals. Following immunosuppression ofC. albicanscolonized mice, competitive fungal commensalism thereby mitigated fatal candidiasis. Metagenome analysis revealedK. weizmanniipresence among human commensals. Our results reveal competitive fungal commensalism within the intestinal microbiota, independent of bacteria and immune responses, that could bear potential therapeutic value for the management ofC. albicans-mediated diseases.
A genuinely hybrid, multiscale 3D cancer invasion and metastasis modelling framework
Authors: Katsaounis Dimitrios , Harbour Nicholas , Williams Thomas , Chaplain Mark , Sfakianakis Nikolaos 
Published: January 2024

AbstractWe introduce in this paper substantial enhancements to a previously proposed hybrid multiscale cancer invasion modelling framework to better reflect the biological reality and dynamics of cancer. These model updates contribute to a more accurate representation of cancer dynamics, they provide deeper insights and enhance our predictive capabilities.Key updates include the integration of porous medium-like diffusion for the evolution of Epithelial-like Cancer Cells and other essential cellular constituents of the system, more realistic modelling of Epithelial-Mesenchymal Transition and Mesenchymal-Epithelial Transition models with the inclusion of Transforming Growth Factor beta within the tumour microenvironment, and the introduction of Compound Poisson Process in the Stochastic Differential Equations that describe the migration behaviour of the Mesenchymal-like Cancer Cells. Another innovative feature of the model is its extension into a multi-organ metastatic framework. This framework connects various organs through a circulatory network, enabling the study of how cancer cells spread to secondary sites.
Recurrent Evolutionary Innovations in Rodent and PrimateSchlafenGenes
Authors: Mordier Joris , Fraisse Marine , Cohen-Tannoudji Michel , Molaro Antoine 
Published: January 2024

ABSTRACTSCHLAFEN proteins are a large family of RNase-related enzymes carrying essential immune and developmental functions. Despite these important roles,Schlafengenes display varying degrees of evolutionary conservation in mammals. While this appears to influence their molecular activities, a detailed understanding of these evolutionary innovations is still lacking. Here, we used in depth phylogenomic approaches to characterize the evolutionary trajectories and selective forces shaping mammalianSchlafengenes. We traced lineage-specificSchlafenamplifications and found that recent duplicates evolved under distinct selective forces, supporting repeated sub-functionalization cycles. Codon-level natural selection analyses in primates and rodents, identified recurrent positive selection over Schlafen protein domains engaged in viral interactions. Combining crystal structures with machine learning predictions, we discovered a novel class of rapidly evolving residues enriched at the contact interface of SCHLAFEN protein dimers. Our results suggest that inter Schlafen compatibilities are under strong selective pressures and are likely to impact their molecular functions. We posit that cycles of genetic conflicts with pathogens and between paralogs drove Schlafens’ recurrent evolutionary innovations in mammals.
C. elegansepicuticlins define specific compartments in the apical extracellular matrix and function in wound repair
Authors: Pooranachithra Murugesan , Jyo Erin M. , Ernst Andreas M. , Chisholm Andrew D. 
Published: January 2024

AbstractThe apical extracellular matrix (aECM) of external epithelia often contains lipid-rich outer layers that contribute to permeability barrier function. The external aECM of nematode is known as the cuticle and contains an external lipid-rich layer, the epicuticle. Epicuticlins are a family of tandem repeat proteins originally identified as components of the insoluble fraction of the cuticular aECM and thought to localize in or near epicuticle. However, there has been littlein vivoanalysis of epicuticlins. Here, we report the localization analysis of the threeC. elegansepicuticlins (EPIC proteins) using fluorescent protein knock-ins to visualize endogenously expressed proteins, and further examine theirin vivofunction using genetic null mutants. By TIRF microscopy, we find that EPIC-1 and EPIC-2 localize to the surface of the cuticle in larval and adult stages in close proximity to the outer lipid layer. EPIC-1 and EPIC-2 also localize to interfacial cuticles and adult-specific cuticle struts. EPIC-3 expression is restricted to the stress-induced dauer stage, where it localizes to interfacial aECM in the buccal cavity. Strikingly, skin wounding in the adult inducesepic-3expression, and EPIC-3::mNG localizes to wound scars. Null mutants lacking one, two, or all three EPIC proteins display reduced survival after skin wounding yet are viable with low penetrance defects in epidermal morphogenesis. Our results suggest EPIC proteins define specific aECM compartments and have roles in wound repair.HighlightsC. elegansepicuticlin (EPIC) proteins localize to specific regions in cortical and interfacial cuticleEpicuticlins colocalize with BLI collagens in struts in adult cuticleEPIC-3 is normally expressed in dauer stage and upregulated by skin woundingMutants lacking all three epicuticlins are viable and show reduced survival after skin wounding
Retinal input is required for the maintenance of neuronal laminae in the ventral lateral geniculate nucleus
Authors: Stebbins Katelyn , Somaiya Rachana Deven , Sabbagh Ubadah , Liang Yanping , Su Jianmin , Fox Michael A. 
Published: January 2024

ABSTRACTRetinal ganglion cell (RGC) axons provide direct input into several nuclei of the mouse visual thalamus, including the dorsal lateral geniculate nucleus (dLGN), which is important for classical image-forming vision, and the ventral lateral geniculate nucleus (vLGN), which is associated with non-image-forming vision. Through both activity- and morphogen-dependent mechanisms, retinal inputs play important roles in the development of dLGN, including the refinement of retinal projections, morphological development of thalamocortical relay cells (TRCs), the timing of corticogeniculate innervation, and the recruitment of inhibitory interneurons from progenitor zones. In contrast, little is known about the role of retinal inputs in the development of vLGN. Grossly, vLGN is divided into two domains, the retinorecipient external vLGN (vLGNe) and the non-retinorecipient internal vLGN (vLGNi). We previously found that vLGNe consists of transcriptionally distinct GABAergic subtypes that are distributed into at least four adjacent laminae. At present, it remains unclear whether retinal inputs influence the development of these cell-specific neuronal laminae in vLGNe. Here, we elucidated the developmental timeline for the formation and maintenance of these laminae in the mouse vLGNe and results indicate that these laminae are specified at or before birth, well before eye-opening and the emergence of experience-dependent visual activity. We observed that mutant mice without retinal inputs have a normal laminar distribution of GABAergic cells at birth; however, after the first week of postnatal development, these mutants exhibited a dramatic disruption in the laminar organization of inhibitory neurons and clear boundaries between vLGNe and vLGNi. Overall, our results show that while the formation of cell type-specific layers in vLGNe does not depend on RGC inputs, retinal signals are critical for their maintenance.
Integrated germline and somatic features reveal divergent immune pathways driving ICB response
Authors: Sears Timothy , Pagadala Meghana , Castro Andrea , Lee Ko-han , Kong JungHo , Tanaka Kairi , Lippman Scott , Zanetti Maurizio , Carter Hannah 
Published: January 2024

AbstractImmune Checkpoint Blockade (ICB) has revolutionized cancer treatment, however mechanisms determining patient response remain poorly understood. Here we used machine learning to predict ICB response from germline and somatic biomarkers and interpreted the learned model to uncover putative mechanisms driving superior outcomes. Patients with higher T follicular helper infiltrates were robust to defects in the class-I Major Histocompatibility Complex (MHC-I). Further investigation uncovered different ICB responses in MHC-I versus MHC-II neoantigen reliant tumors across patients. Despite similar response rates, MHC-II reliant responses were associated with significantly longer durable clinical benefit (Discovery: Median OS=63.6 vs. 34.5 months P=0.0074; Validation: Median OS=37.5 vs. 33.1 months, P=0.040). Characteristics of the tumor immune microenvironment reflected MHC neoantigen reliance, and analysis of immune checkpoints revealed LAG3 as a potential target in MHC-II but not MHC-I reliant responses. This study highlights the value of interpretable machine learning models in elucidating the biological basis of therapy responses.Statement of SignificanceImmune checkpoint blockade works only in a fraction of patients for reasons that are still not fully understood. Our study reveals heterogeneity in the immune responses of ICB responders that correlates with characteristics of the neoantigen landscape. This heterogeneity is accompanied by differences in the duration of clinical benefit as well as by differences as to which immune checkpoint gene serves as a biomarker of ICB response. These findings suggest possible new strategies for improving ICB responses.HighlightsWe used machine learning to study ICB response across 708 patients from 8 studies across 3 tumor types (melanoma, RCC, and NSCLC).Combining germline and somatic features improves prediction of ICB responseInteractions between germline and somatic features reveal mechanisms contributing to ICB sensitivity.MHC-I vs. MHC-II reliance implicates LAG3 as a prognostic biomarker in the context of CD4 T cell driven responses.MHC-II neoantigen reliant responses provide superior durable clinical benefit in response to ICB.
Inhibition of Alpha Interferon-Induced miR-873 Negatively Affects the Hepatitis B Virus Expression
Authors: Zhou Mingsha , Xing Liu , Fan Jie , Zhao Mingming , Chen Lijuan , Luo Jia , Li Shan , Luo Pan , Duan Yong , Zhou Li 
Published: January 2024

AbstractBackgroundAlpha interferon (IFN-α)-based therapy can effectively treat chronic hepatitis B virus (HBV) infection, which remains a serious public health problem. This study aims to identify the potential biomarker of IFN treatment and investigate the effects of miR-873 on chronic hepatitis B (CHB).MethodsWe utilized the random forest to screen core differentially expressed miRNAs (DEmiRNAs) based on the miRNA (GSE29911) dataset. DEmiRNAs expressions were determined in clinical samples from CHB patients and normal controls. HBV-transfected hepatoma cell lines were constructed for vitro study. Quantitative real-time reverse transcription PCR (RT-qPCR) was used to determine miRNA mRNA expressions. ELISA assays were used to detect the secretion levels of HBsAg and HBeAg.ResultsBoruta feature selection revealed miR-873 hinting at a predictive marker for IFN response. MiR-873 was significantly up-regulated in the CHB patients, as compared with normal controls (P<0.001). Increased expression of miR-873 was also found in HBV-infected cells (P<0.001). With IFN-α treatment, miR-873 was significantly down-regulated in HBV-infected Huh-7 and HepG-NTCP cells (P<0.05). IFN-α treatment and miR-873 inhibitor significantly reduced HBsAg and HBeAg level (P<0.05). The inhibitory effect was enhanced by blocking the IFN-α-induced miR-873 downregulation by inhibitor transfection (P<0.05). In miR-873 mimic-treated cells, the inhibitory effect was greatly supressed by blocking the IFN-α-induced miR-873 downregulation by mimic transfection (P< 0.01).ConclusionWe provide evidence that inhibition of miR-873 by IFN-α enhances the antiviral effects of IFN-α. Our study provides a potential strategy to enhance the anti-HBV effect of IFN-α by inhibiting miR-873 expression.
Obesity Human Soluble Prorenin Receptor Expressed in Adipose Tissue Improves Insulin Sensitivity and Endothelial Function in Obese Female Mice
Authors: Arthur Gertrude , Ahmed Nermin , Nichols Kellea , Poupeau Audrey , Collins Katelyn , Lindner Volkhard , Loria Analia 
Published: January 2024

ABSTRACTSoluble prorenin receptor (sPRR) is a component of the renin-angiotensin system (RAS) identified as a plasma biomarker for human metabolic disease. However, what tissue source of sPRR is implicated in the modulation of metabolic function remains unclear. This study investigated the contribution of human sPRR (HsPRR) produced in the adipose tissue (Adi) on the metabolic and cardiovascular function of lean and obese male and female mice. Adi-HsPRR mice, generated by crossing human sPRR-Myc-tag and Adiponectin/Cre mice, were fed a low-fat or high-fat diet (10% and 60% kCal from fat, respectively) for 20 weeks. Obese Adi-HsPRR mice showed elevated sPRR levels in adipose tissue without affecting adipocyte size or fat depot weight. Despite plasma sPRR being similar between obese Adi-HsPRR and control female mice, a positive correlation between plasma sPRR and adiposity was present only in controls. Obese Adi-HsPRR male mice showed elevated plasma sPRR compared with controls, but no correlation with adiposity was found in either group. Nevertheless, Adi-HsPRR expression improved insulin sensitivity and endothelial function, reduced adipogenic genes mRNA abundance (PPARg, SEBP1C and CD36), and increased plasma Angiotensin 1-7 levels only in obese HsPPR female mice. Taken together, elevated HsPRR in adipose tissue improved metabolic and vascular function in obese female mice despite normal circulating levels of sPRR, whereas increased local and circulating levels of HsPRR did not influence metabolic and cardiovascular function in obese male mice. Our data suggest that increased plasma sPRR associated with metabolic disease could be produced by other tissues rather than adipocytes.
Psychological and social risk factors and pregnancy outcome: a prospective cohort study
Authors: Schipper Elbert-Jaap I. , Wardenaar Klaas J. , Bolte Annemieke C. , Monden Rei , van Os Titus W.D.P. , Wichers Marieke , de Jonge Peter 
Published: January 2024

AbstractBackgroundResearch suggests that besides somatic factors, psychological and social factors are associated with pregnancy outcomes. The objective of this study was to determine the independent effects of psychosocial risk factors on maternal blood pressure, gestational age at birth, birthweight and Apgar score.MethodsIn a prospective cohort study, Dutch women in the first half of pregnancy were recruited at a regional hospital, a university hospital and ten midwife practices. At inclusion, participants (before 20 weeks of gestation) filled in questionnaires on social and psychological factors. Obstetric data were extracted from patient records. Associations between risk factors and pregnancy outcomes were analysed with multivariable linear and logistic regression.Results598 Women were included in the study. 14 Women did not return questionnaires and 12 women stopped study participation before delivery. In multivariable regression analysis, primiparity, Odds Ratio [OR] = 3.4 (1.5, 7.5), obstetric and somatic history, OR = 3.5 (1.5, 7.9), and diastolic blood pressure at intake, OR = 1.1 (1.0, 1.1), were independently associated with preterm delivery. Smoking status, OR = 5.5 (2.3, 13), was independently associated with a newborn small for gestational age, and primiparity, OR = 6.9 (1.1, 45), with a low Apgar score. Diastolic blood pressure at intake, OR = 1.1 (1.07, 1.14), hypertension at intake, OR = 3.6 (1.1, 11), and negative affect, OR = 1.1 (1.02, 1.14), were independently associated with gestational hypertension. Negative affect was the only psychosocial risk factor independently associated with pregnancy outcome.ConclusionAlthough psychosocial factors are important in obstetric care, measurement of these factors in early pregnancy seems to have limited independent predictive value for adverse pregnancy outcome when medical and/or obstetric history and commonly applied physical measurements are already considered.
Factors influencing perceived usefulness of a branded weight-loss app
Authors: Martin-Vicario Lara , Martínez-Sánchez María Eugenia , Nicolas-Sans Ruben 
Published: January 2024

PurposeThe aim of this study was to observe how a user’s individual factors in a commercial weight-loss treatment app affect their perceived usefulness of its features and how they relate to each other.Design/methodology/approachThe information was obtained from an online survey with a sample of 412 users from a branded app for a commercial weight-loss treatment using body mass index (BMI), self-efficacy, social support and perceived usefulness as variables.FindingsUsers with higher self-efficacy perceived the app’s features as more useful. However, BMI was not a factor except for the psycho-emotional support features, which individuals with obesity perceived as more useful. Likewise, it was found that there weren’t any significant differences in self-efficacy based on their BMI. Lastly, it was found that social support could not be used as a factor to predict self-efficacy.Research limitations/implicationsThis study helps understand how individual factors for behavioural change may affect the perceived usefulness of a weight-loss app. Furthermore, the significance of self-efficacy as an influencing factor provides useful information for companies and app developers alike when developing their branded apps.Originality/valueThis study contributes to the body of knowledge on factors affecting user perceptions of weight-loss apps. It also adds to the literature of branded apps as complimentary resources for companies, which has not been studied in detail.
Experience-driven well-being: the case of unmanned smart hotels
Authors: Sthapit Erose , Ji Chunli , Ping Yang , Prentice Catherine , Garrod Brian , Yang Huijun 
Published: January 2024

Purpose
Drawing on the theory of memory-dominant logic, this study aims to examine how the substantive staging of the servicescape, experience co-creation, experiential satisfaction and experience intensification affect experience memorability and hedonic well-being in the case of unmanned smart hotels.

Design/methodology/approach
An online survey was used, with the target respondents being hotel guests people aged 18 years and older who had been recent guests of the FlyZoo Hotel in Hangzhou, China. Data were collected online from 429 guests who had stayed in the hotel between April and June 2023. Data analysis was undertaken using structural equation modelling.

Findings
The results suggest that all the proposed four constructs are positive drivers of a memorable unmanned smart hotel experience. The relationship between the memorability of the hotel experience and hedonic well-being was found to be significant and positive.

Practical implications
Unmanned smart hotels should ensure that all smart technologies function effectively and dependably and offer highly personalised services to guests, allowing them to co-create their experiences. This will lead to the guest receiving a satisfying and memorable experience. To enable experience co-creation using smart technologies, unmanned smart hotels could provide short instructional videos for guests, as well as work closely with manufacturers and suppliers to ensure that smart technology systems are regularly updated.

Originality/value
This study investigates the antecedents and outcomes of a novel phenomenon and extends the concept of memorable tourism experiences to the context of unmanned smart hotels.