bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negative Life Events and Epigenetic Ageing: a Study in the Netherlands Twin Register
Authors: Gonggrijp B.M.A. , van de Weijer S.G.A. , Bijleveld C.C.J.H. , Boomsma D.I. , van Dongen J. 
Published: February 2024

AbstractWe aimed to understand the long-term impact of negative life events (NLE) on epigenetic aging in 1,808 adults from the Netherlands Twin Register, analyzing five epigenetic biomarkers (Hannum, Horvath, PhenoAge, GrimAge, DunedinPACE) and a series of NLE, including victimization and economic hardship. In population-level analyses, associations between a higher number of NLE (particularly financial adversities, sexual crimes, and job loss) were seen for GrimAge and DunedinPACE biomarkers. The association between the number of NLE and financial problems and epigenetic age acceleration measured by the GrimAge biomarker persisted after adjusting for BMI, smoking, and white blood cell counts. In monozygotic twin pairs discordant for NLE (274 pairs) the associations were diminished, indicating that the population associations may be confounded by shared familial (genetic and environmental) factors. These findings underscore the intricate link between environmental stressors and biological aging, stressing the need for comprehensive studies considering both genetic and environmental influences.
Dissociable roles of neural pattern reactivation and transformation during recognition of words read aloud and silently: An MVPA study of the production effect
Authors: Bailey Lyam M. , Matheson Heath E. , Fawcett Jonathon M. , Bodner Glen E. , Newman Aaron J. 
Published: February 2024

AbstractRecent work surrounding the neural correlates of episodic memory retrieval has focussed on the decodability of neural activation patterns elicited by unique stimuli. Research in this area has revealed two distinct phenomena: (i) neural pattern reactivation, which describes the fidelity of activation patterns between encoding and retrieval; (ii) neural pattern transformation, which describes systematic changes to these patterns. This study used fMRI to investigate the roles of these two processes in the context of the production effect, which is a robust episodic memory advantage for words read aloud compared to words read silently. Twenty-five participants read words either aloud or silently, and later performed old-new recognition judgements on all previously seen words. We applied multivariate analysis to compare measures of reactivation and transformation between the two conditions. We found that, compared with silent words, successful recognition of aloud words was associated with reactivation in the left insula and transformation in the left precuneus. By contrast, recognising silent words (compared to aloud) was associated with relatively more extensive reactivation, predominantly in left ventral temporal and prefrontal areas. We suggest that recognition of aloud words might depend on retrieval and metacognitive evaluation of speech-related information that was elicited during the initial encoding experience, while recognition of silent words is more dependent on reinstatement of visual-orthographic information. Overall, our results demonstrate that different encoding conditions may give rise to dissociable neural mechanisms supporting single word recognition.
Unraveling the Role of Urea Hydrolysis in Salt Stress Response during Seed Germination and Seedling Growth inArabidopsis thaliana
Authors: Bu Yuanyuan , Dong Xingye , Zhang Rongrong , Shen Xianglian , Liu Yan , Wang Shu , Takano Tetsuo , Liu Shenkui 
Published: February 2024

AbstractUrea is intensively utilized as a nitrogen fertilizer in agriculture, originating either from root uptake or from catabolism of arginine by arginase. Despite its extensive use, the underlying physiological mechanisms of urea, particularly its adverse effects on seed germination and seedling growth under salt stress remains unclear. In this study, we demonstrate that salt stress induces excessive hydrolysis of arginine-derived urea, leading to an increase in cytoplasmic pH within seed radical cells, which, in turn, triggers salt-induced inhibition of seed germination (SISG) and hampers seedling growth. Our findings challenge the long-held belief that ammonium accumulation and toxicity are the primary causes of SISG, offering a novel perspective on the mechanism underlying these processes. This study provides significant insights into the physiological impact of urea hydrolysis under salt stress, contributing to a better understanding of SISG.
Multi-gradient Permutation Survival Analysis Identifies Mitosis and Immune Signatures Steadily Associated with Cancer Patient Prognosis
Authors: Cai Xinlei , Ye Yi , Liu Xiaoping , Fang Zhaoyuan , Chen Luonan , Li Fei , Ji Hongbin 
Published: February 2024

AbstractThe inconsistency of the association between genes and cancer prognosis is often attributed to many variables that contribute to patient survival. Whether there exist the Genes Steadily Associated with Prognosis (GEARs) and what their functions are remain largely elusive. We have developed a novel method called “Multi-gradient Permutation Survival Analysis” (MEMORY) to screen the GEARs using RNA-seq data from the TCGA database. Then we employed a network construction approach to identify hub genes from GEARs, and utilized them for cancer classification. In the case of LUAD, the GEARs were found to be related to mitosis. Our analysis suggested that LUAD cell lines carryingPIK3CAmutations exhibit increased drug resistance. For BRCA, the GEARs were related to immunity. The analysis revealed thatCDH1mutation might influence immune infiltration through the EMT process in BRCA. We further explored the prognostic relevance of mitosis and immunity through their respective scores. This study offers significant biological insights into GEARs and highlights their potential as robust prognostic indicators across diverse cancer types.
Prenatal VEGF Nano-Delivery Reverses Congenital Diaphragmatic Hernia-Associated Pulmonary Abnormalities
Authors: Loukogeorgakis Stavros P. , Michielin Federica , Al-Juffali Noura , Jimenez Julio , Shibuya Soichi , Allen-Hyttinen Jessica , Eastwood Patrice , Alhendi Ahmed S.N. , Davidson Joseph , Naldi Eleonora , Maghsoudlou Panagiotis , Tedeschi Alfonso , Khalaf Sahira , Khabbush Aziza , Plate Manuela , Fachin Camila , Dias Andre Dos Santos , Sindhwani Nikhil , Scaglioni Dominic , Xenakis Theodoros , Sebire Neil , Giomo Monica , Eaton Simon , Toelen Jaan , Luni Camilla , Pavan Piero , Carmeliet Peter , Russo Francesca , Janes Samuel , Nikolic Marko Z. , Elvassore Nicola , Deprest Jan , Coppi Paolo De 
Published: February 2024

AbstractRationaleCongenital diaphragmatic hernia (CDH) results in lung hypoplasia. In severe cases, tracheal occlusion (TO) can be offered to promote lung growth. However the benefit is limited, and novel treatments are required to supplement TO. Vascular endothelial growth factor (VEGF) is downregulated in animal models of CDH and could be a therapeutic target, but its role in human CDH is not known.ObjectivesTo investigate whether VEGF supplementation could be a suitable treatment for CDH-associated lung pathology.MethodsFetal lungs from CDH patients were used to determine pulmonary morphology and VEGF expression. A novel humanex vivomodel of fetal lung compression recapitulating CDH features was developed and used to determine the effect of exogenous VEGF supplementation (Figure 1A). A nanoparticle-based approach for intra-pulmonary delivery of VEGF was developed by conjugating it on functionalized nanodiamonds (ND-VEGF) and was tested in experimental CDHin vivo.Measurements and Main ResultsVEGF expression was downregulated in distal pulmonary epithelium of human CDH fetuses in conjunction with attenuated cell proliferation. The compression model resulted in impaired branching morphogenesis similar to CDH and downregulation of VEGF expression in conjunction with reduced proliferation of terminal bud epithelial progenitors; these could be reversed by exogenous supplementation of VEGF. Prenatal delivery of VEGF with the ND-VEGF platform in CDH fetal rats resulted in lung growth and pulmonary arterial remodelling that was complementary to that achieved by TO alone with appearances comparable to healthy controls.ConclusionsThis innovative approach could have a significant impact on the treatment of CDH.
DO ORGANIC, CONVENTIONAL, AND INTENSIVE APPROACHES IN LIVESTOCK FARMING HAVE AN IMPACT ON THE CIRCULATION OF INFECTIOUS AGENTS? A SYSTEMATIC REVIEW, FOCUSED ON DAIRY CATTLE
Authors: Pajoro Massimo , Brilli Matteo , Pezzali Giulia , Kramer Laura , Moroni Paolo , Bandi Claudio 
Published: February 2024

ABSTRACTA common thought is that extensive and organic breeding systems are associated with lower prevalence of infections in livestock animals, compared to intensive ones. In addition, organic systems limit the use of antimicrobial drugs, which may lead to lower emergence of antimicrobial resistances (AMR). To examine these issues, avoiding any a priori bias, we carried out a systematic literature search on dairy cattle breeding. Search was targeted to publications that compared different types of livestock farming (intensive, extensive, conventional, organic) in terms of the circulation of infectious diseases and AMR. A total of 101 papers were finally selected. These papers did not show any trend in the circulation of the infections in the four types of breeding systems. However, AMR was more prevalent on conventional dairy farms compared to organic ones. The prevalence of specific pathogens and types of resistances were frequently associated with specific risk factors that were not strictly related to the type of farming system. In conclusion, we did not find any evidence suggesting that extensive and organic dairy farming bears any advantage over the intensive and conventional ones, in terms of the circulation of infectious agents.
RNA dicing regulates the expression of an oncogenic JAK1 isoform
Authors: Malka Yuval , van der Kammen Rob , Ju Shinyeong , Alkan Ferhat , Lee Cheolju , Faller William James 
Published: February 2024

AbstractmRNA transcripts have limited potential for protein synthesis, defined by their open reading frames1. However, recent advances have revealed a far more complex reality, in which the proteome exceeds the perceived limits of the transcriptome2–6exposing a significant gap in our understanding. Our prior studies have demonstrated that mRNA can undergo further processing, yielding truncated, uncapped mRNAs with translation potential2,7. Yet, the biological importance of this process remains mostly unclear. Here, we demonstrate that cleavage within the coding sequence of JAK1 mRNA produces an uncapped variant downstream to the cleavage site, at the expense of the full-length transcript. This results in the independent translation of the JH1 kinase domain, a process we term ‘RNA dicing’. Notably, canonical and diced JAK1 variants have distinct impacts on cell proliferation and tumorigenesis, operating independently, localizing to distinct cellular compartments. In addition, the activation of JAK1 signaling through IFNγ induction promotes the dicing of JAK1, thereby altering the balance of isoforms present. Base editor screens reveal that stop-codon nonsense mutations, which are typically considered loss-of-function, have differing impacts depending on their position relative to the dicing site. In agreement with this, JAK1 nonsense frameshift (JAK1fs) mutations in endometrial tumors inhibit the tumor-suppressive functions of canonical JAK1, while amplifying the oncogenic potential of the diced JH1 kinase domain. Lastly, we demonstrate that Momelotinib8, a JAK1-specific inhibitor, is more effective in cancer cells carrying a “loss-of-function” JAK1fs mutation, highlighting the significant impact of RNA dicing biology as a potent tool for patient stratification. Our findings characterize RNA dicing as a fundamental regulatory machinery that diversifies the potential products of a single mRNA molecule, and allows for significant variation in biological function.
Using runs of homozygosity and machine learning to disentangle sources of inbreeding and infer self-fertilization rates
Authors: Zeitler Leo , Gilbert Kimberly J. 
Published: February 2024

AbstractRuns of homozygosity (ROHs) are indicative of elevated homozygosity and inbreeding due to mating of closely related individuals. Self-fertilization can be a major source of inbreeding which elevates genomewide homozygosity and thus should also create long ROHs. While ROHs are frequently used to understand inbreeding in the context of conservation and selective breeding, as well as for consanguinity of populations and their demographic history, it remains unclear how ROH characteristics are altered by selfing and if this confounds expected signatures of inbreeding due to demographic change. Using simulations, we study the impact of the mode of reproduction and demographic history on ROHs. We apply random forests to identify unique characteristics of ROHs, indicative of different sources of inbreeding. We pinpoint distinct features of ROHs that can be used to better characterize the type of inbreeding the population was subjected to and to predict outcrossing rates and complex demographic histories. Using additional simulations and four empirical datasets, two from highly selfing species and two from mixedmaters, we predict the selfing rate and validate our estimations. We find that self-fertilization rates are successfully identified even with complex demography. Population genetic summary statistics improve algorithm accuracy particularly in the presence of additional inbreeding, e.g., from population bottlenecks. Our findings highlight the importance of ROHs in disentangling confounding factors related to various sources of inbreeding and demonstrate situations where such sources cannot be differentiated. Additionally, our random forest models provide a novel tool to the community for inferring selfing rates using genomic data.
Exposure assessment suggests some cytotoxicBacillus cereusgroup genotypes can grow over 3 logs in HTST milk throughout the shelf life at temperature abuse conditions
Authors: Su Jun , Chandross-Cohen Tyler , Qian Chenhao , Carroll Laura , Kimble Kayla , Yount Mackenna , Wiedmann Martin , Kovac Jasna 
Published: February 2024

ABSTRACTCytotoxicBacillus cereusgroup strains are common causes of foodborne illness including diarrhea. However, our ability to assess food safety risks associated with the exposure to cytotoxicB. cereusgroup strainsviacontaminated food is limited due to the lack of predictive tools. In this study, we experimentally quantified the growth of 17 cytotoxicB. cereusgroup strains, representing six phylogenetic groups, in skim milk broth and used the growth data to develop an exposure assessment model. While none of the tested strains showed detectable growth in HTST milk at 4 or 6°C, 15 of the 17 strains showed growth at 10°C, 1 of the 17 strains showed growth at 8°C, and all strains grew at ≥14°C. Growth data for 16 strains allowed us to generate linear secondary growth models, which were then used to develop the exposure assessment model. We simulated a five-stage supply chain with up to 35 consumer storage days, as that was the timing when distinguishable variations in percent milk containers over 105CFU/m with differentB. cereusgenotypes were observed. When the initial contamination level of the HTST milk is set at an average of 100 CFU/mL, the model predicts that, on consumer home storage day 21 and 35, 2.81±0.66 and 4.13±2.53 % (mean ± standard deviation) of the milk containers would exceedB. cereusgroup concentrations of 105CFU/mL; these data represent the average across all strains. Sensitivity analysis showed that variation in the input parameter Q0, the initial physiological state of cells, has the largest effect on model’s prediction for 1 of 4 group II isolates, 1 of 6 group IV isolates and both group V isolates, suggesting the need to better characterize the growth parameters of these isolates. What-if scenario analysis showed that increased mean and variability in storage temperature at the consumer’s home both have substantial influence on final predictedB. cereusgroup concentration in milk containers. This model introduces an initial tool designed to facilitate risk-based food safety decision making for products that are contaminated with lowB. cereusgroup levels.
p300 KAT regulates SOX10 stability and function in human melanoma
Authors: Waddell Aaron , Grbic Nicole , Leibowitz Kassidy , Wyant W. Austin , Choudhury Sabah , Park Kihyun , Collard Marianne , Cole Philip A. , Alani Rhoda M. 
Published: February 2024

AbstractSOX10 is a lineage-specific transcription factor critical for melanoma tumor growth, while SOX10 loss-of-function drives the emergence of therapy-resistant, invasive melanoma phenotypes. A major challenge has been developing therapeutic strategies targeting SOX10’s role in melanoma proliferation, while preventing a concomitant increase in tumor cell invasion. Here, we report that the lysine acetyltransferase (KAT)EP300andSOX10gene loci on Chromosome 22 are frequently co-amplified in melanomas, including UV-associated and acral tumors. We further show that p300 KAT activity mediates SOX10 protein stability and that the p300 inhibitor, A-485, downregulates SOX10 protein levels in melanoma cells via proteasome-mediated degradation. Additionally, A-485 potently inhibits proliferation of SOX10+ melanoma cells while decreasing invasion in AXLhigh/MITFlowmelanoma cells through downregulation of metastasis-related genes. We conclude that the SOX10/p300 axis is critical to melanoma growth and invasion, and that inhibition of p300 KAT activity through A-485 may be a worthwhile therapeutic approach for SOX10-reliant tumors.
Liver-innervating vagal sensory neurons are indispensable for the development of hepatic steatosis and anxiety-like behavior in diet-induced obese mice
Authors: Hwang Jiyeon , Lee Sangbhin , Okada Junichi , Liu Li , Pessin Jeffrey E. , Chua Streamson C. , Schwartz Gary J. , Jo Young-Hwan 
Published: February 2024

AbstractThe visceral organ-brain axis, mediated by vagal sensory neurons, is essential for maintaining various physiological functions. Here, we investigate the impact of liver-projecting vagal sensory neurons on energy balance, hepatic steatosis, and anxiety-like behavior in mice under obesogenic conditions. A small subset of vagal sensory neurons in both the left and right ganglia innervate the liver and project centrally to the nucleus of the tractus solitarius, area postrema, and dorsal motor nucleus of the vagus, and peripherally to the periportal areas in the liver. Surprisingly, the loss of liver-projecting vagal sensory neurons via caspase-induced selective destruction of advillin-positive neurons prevents diet-induced obesity, and these outcomes are associated with increased energy expenditure. Although males and females exhibit improved glucose homeostasis following disruption of liver-projecting vagal sensory neurons, only male mice display increased insulin sensitivity. Furthermore, the loss of liver-projecting vagal sensory neurons limits the progression of hepatic steatosis in mice fed a steatogenic diet. Intriguingly, mice lacking liver-innervating vagal sensory neurons also exhibit less anxiety-like behavior compared to control mice. Therefore, modulation of the liver-brain axis may aid in designing effective treatments for both psychiatric and metabolic disorders associated with obesity and MAFLD.
Development of a 3Din vitrohuman-sized model of cervical dysplasia to evaluate the delivery of ethyl cellulose-ethanol injection for the treatment of cervical dysplasia ablation
Authors: Cadena Ines A , Adhikari Gatha , Almer Alyssa , Jenne Molly , Obasi Ndubuisi , Zurita Nicolas F. Soria , Rochefort Willie E , Mueller Jenna L. , Fogg Kaitlin C. 
Published: February 2024

AbstractCervical cancer, the second leading cause of cancer-related death for women worldwide, remains a preventable yet persistent disease that disproportionately affects women in low and middle-income countries (LMICs). While existing therapies for treating cervical dysplasia are effective, they are often inaccessible in LMICs. Ethanol ablation is an alternative low-cost, accessible therapy that we previously enhanced into an ethyl cellulose (EC)-ethanol gel formulation to improve efficacy. When seeking to evaluate EC-ethanol for cervical dysplasia, we found a paucity of relevant animal models. Thus, in this study, we developed a 3Din vitromodel of cervical dysplasia featuring a central lesion of cervical cancer cells surrounded by fibroblasts and keratinocytes to enable the evaluation of EC-ethanol and other novel therapeutics. Our GelMA-based 3D model successfully captured the architectural complexity of cervical dysplasia, showcasing cell response and high viability. The GelMA hydrogel formulation (8.7% w/v) exhibited viscoelastic properties akin to human cervical tissue. Using micro-CT imaging, we assessed EC-ethanol injection deposition in the hydrogel, revealing retention of virtually the entire injected volume near the injection site. Finally, we evaluated the EC-ethanol injection’s efficacy in eliminating cervical cancer cells. The EC-ethanol injection led to a significant decrease in cancer cell viability while preserving healthy cells in the 3Din vitromodel. Taken together, ourin vitromodel mirrored the architecture of cervical dysplasia and demonstrated the potential of EC-ethanol for localized treatment of cervical dysplasia.