bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-tissue transition of A-to-I RNA editing pattern and its regulatory relevance in transcription, splicing, and translation during development
Authors: Pan Jia-Qi , Pan Xu-Bin , Liu Yan-Shan , Jin Yun-Yun , Chen Jian-Huan 
Published: February 2024

AbstractPrevious studies have shown that A-to-I RNA editing can occur in various organs and tissues of normal physiological conditions. However, the dynamics of RNA editing and its functional relevance in multiple tissues and organs during the embryo-to-adult transition in mammals remains to be elucidated. Herein, we performed a comprehensive analysis of RNA sequencing and ribosome profiling of six mouse tissues at embryonic and adult stages, to elucidate the tissue- and stage-specific landscape of A-to-I RNA editing. Our result identified transcriptome-wide A-to-I RNA editing in six tissue types. Furthermore, differential expression was concurrently observed in a set of distinct differential RNA editing genes at both mRNA and protein levels across different tissues. Gene function and pathway enrichment analysis indicated that these genes with both differential editing and expression were involved in not only tissue-specific biological functions, but also common fundamental processes of post-transcriptional and post-translational modification. Further analysis showed a dynamic interaction between A-to-I RNA editing and alternative splicing in cell survival, death, signal transduction, and cell-cell interactions during development. Overall, our study demonstrates the potential role played by A-to-I editing during development, providing new insight into the effects of RNA editing within both transcriptional and translational landscape on it.
Social touch shapes communication and animal recognition in naked mole-rats
Authors: Schwark Ryan , Ogundare Simon , Sheng Preston , Foster William , Chang Phalaen , Tsai Yu-Young , Arnold Amanda , Abdus-Saboor Ishmail 
Published: February 2024

SummaryThe East African naked mole-rat (Heterocephalus glaber) lives in cooperative subterranean colonies and displays a capacity to recognize social novelty, rank, and identity. The sensory cues used for social recognition remain poorly understood, especially because many of their senses are either lost or greatly reduced in comparison to other mammals. Here, we found that naked mole-rats actively touch faces 100% of the time they encounter one another in a tunnel test, followed by milliseconds speed determination of the rank of the other animal. Even in an open arena, naked mole-rats engage in face-to-face touch hundreds of times in a 10-minute social pairing and colonies do so tens of thousands of times over a 24-hour period in their home environment. To demonstrate the prominence of face touch at a molecular level, we show that social housing conditions lead to widespread activation of mechanosensory ion channels, including Piezo2, in neurons that innervate the face, but not the body. Lastly, to determine the ethological relevance of face touch, we reduced its capacity with facial whisker trimming and revealed an apparent inability for animals to recognize colony members. Together, these findings uncover face touch as a prominent social behavior in naked mole-rats that is intimately linked to social recognition.
A modular toolkit for environmentalRhodococcus, Gordonia, andNocardiaenables complex metabolic manipulation
Authors: Jansen Zachary , Alameri Abdulaziz , Wei Qiyao , Kulhanek Devon L. , Gilmour Andrew R. , Halper Sean , Schwalm Nathan D. , Thyer Ross 
Published: February 2024

ABSTRACTSoil-dwelling Actinomycetes are a diverse and ubiquitous component of the global microbiome, but largely lack genetic tools comparable to those available in model species such asE. coliorPseudomonas putida, posing a fundamental barrier to their characterization and utilization as hosts for biotechnology. To address this, we have developed a modular plasmid assembly framework along with a series of genetic control elements for the previously genetically intractable Gram-positive environmental isolateRhodococcus ruberC208 and demonstrate conserved functionality in diverse environmental isolates ofRhodococcus, NocardiaandGordonia. This toolkit encompasses Mycobacteriale origins of replication, broad-host range antibiotic resistance markers, transcriptional and translational control elements, fluorescent reporters, a tetracycline-inducible system, and a counter-selectable marker. We use this toolkit to interrogate the carotenoid biosynthesis pathway inRhodococcus erythropolisN9T-4, a weakly carotenogenic environmental isolate and engineer higher pathway flux towards the keto-carotenoid canthaxanthin. This work establishes several new genetic tools for environmental Mycobacteriales and provides a synthetic biology framework to support the design of complex genetic circuits in these species.IMPORTANCESoil-dwelling Actinomycetes, particularly the Mycobacteriales, include both diverse new hosts for sustainable biomanufacturing and emerging opportunistic pathogens.Rhodococcus, GordoniaandNocardiaare three abundant genera with particularly flexible metabolisms and untapped potential for natural product discovery. Among these,Rhodococcus ruberC208 was shown to degrade polyethylene,Gordonia paraffinivoranscan assimilate carbon from solid hydrocarbons, andNocardia neocaledoniensis(and many otherNocardia) possesses dual isoprenoid biosynthesis pathways. Many species accumulate high levels of carotenoid pigments, indicative of highly active isoprenoid biosynthesis pathways which may be harnessed for fermentation of terpenes and other commodity isoprenoids. Modular genetic toolkits have proven valuable for both fundamental and applied research in model organisms, but such tools are lacking for most Actinomycetes. Our suite of genetic tools and DNA assembly framework were developed for broad functionality and to facilitate rapid prototyping of genetic constructs in these organisms.
Endovascular thrombectomy with and without preceding thrombolysis in posterior circulation stroke – insights from STAR
Authors: Heide Ev-Christin , Al Kasab Sami , Alawieh Ali , Arthur Adam , Brinjikji Waleed , Chowdhry Shakeel , Crosa Roberto , Cuellar Hugo , De Leacy Reade , Dumont Travis , Ernst Marielle , Ezzeldin Mohamad , Fragata Isabel , Howard Brian , Jabbour Pascal , Kan Peter , Kim Joon-Tae , Levitt Michael R. , Mascitelli Justin , Matouk Charles , Moss Mark , Navia Pedro , Osbun Joshua , Park Min S. , Polifka Adam , Psychogios Marios-Nikos , Rai Ansaar , Romano Daniele G. , Shaban Amir , Starke Robert M. , Tanweer Omar , Williamson Richard , Wolfe Stacey Q. , Yoshimura Shinichi , Spiotta Alejandro M. , Maier Ilko L. 
Published: February 2024

AbstractBackgroundMultiple randomized trials could not establish the non-inferiority of endovascular thrombectomy (EVT) alone without preceding intravenous thrombolysis (IVT) or superiority of IVT followed by EVT in anterior circulation large vessel occlusion (LVO) stroke. The role of prior IVT in posterior circulation LVO remains controversial.MethodsIn this multicenter, retrospective study, stroke patients with LVO in the posterior circulation who received EVT alone or with IVT were selected from the stroke thrombectomy and aneurysm registry (STAR) between 2013 to 2022. Effects of IVT followed by thrombectomy on favorable functional outcome (defined as modified Rankin scale ≤ 3 at 90 days) and safety were investigated using multivariable logistic and linear regression models.ResultsOf the 588 included patients, 67 % (n = 394) were treated with EVT alone and 29% (n = 170) with EVT after IVT and 4% (n = 24) have missing values on this variable. Controlling for multiple confounding factors, IVT was not associated with a higher likelihood of favorable functional outcome at 90 days (odds ratio 1.04, 95 % CI 0.52-2.09, p = 0.901). Thrombectomy alone did not show any safety advantages compared with those receiving IVT.ConclusionsSimilar functional outcomes and complication rates were seen in patients with posterior circulation LVO treated with EVT alone vs EVT after IVT. Further prospective studies are required to determine the utility of IVT in posterior circulation stroke, especially in patients being directly admitted to thrombectomy centers.
Time Resolved Inspection of Ionizable-Lipid Facilitated Lipid Nanoparticle Disintegration and Cargo Release at an Endosomal Membrane Mimic
Authors: Aliakbarinodehi Nima , Niederkofler Simon , Olsén Erik , Jing Yujia , Emilsson Gustav , Sjöberg Mattias , Agnarsson Björn , Lindfors Lennart , Höök Fredrik 
Published: February 2024

ABSTRACTThis study investigates pH-triggered fusion dynamics of lipid nanoparticles (LNPs) with an endosomal membrane mimic, addressing mechanistic aspects of a crucial yet elusive process for effective mRNA delivery. Utilizing time-resolved total internal reflection fluorescence (TIRF) imaging, we observed a delayed onset of LNP fusion upon pH drop, lasting seconds to minutes depending on pH and LNP size. Once initiated, LNP fusion and cargo escape occurred rapidly within tens to hundreds of milliseconds. While LNP disintegration is observed to lead to release of a significant portion of mRNA into the acidic environment, some mRNA molecules remained mobile on the endosomal membrane mimic due to deprotonation-resistant complex salt formation. Comparison of the fusion efficiency of two LNP formulations correlated with protein translation in human primary cell transfection data, emphasizing the importance of biophysical investigations in understanding ionizable-lipid-containing LNP-assisted mRNA delivery mechanisms and providing insights for optimizing mRNA-LNP design for enhanced endosomal escape.
Capturing and Characterising Wild Yeast for Beer Brewing
Authors: Kerr Edward D. , Howes Mark T. , Schulz Benjamin L. 
Published: February 2024

AbstractBeer is typically made using fermentation withSaccharomyces cerevisiaeorSaccharomyces pastorianus, domesticated brewing yeasts. Historically, wild, non-Saccharomycesyeasts have also been frequently used in mixed culture fermentations to provide interesting and unique flavours to beer. However, brewing using mixed cultures or by spontaneous fermentation makes reproducing flavours and beer styles extremely difficult. Here, we describe a pipeline from collection of wild yeast from plant material to the characterisation and industrial scale production of beer using wild yeast. We isolated and identified wild yeast strains from the St Lucia campus of The University of Queensland, Brisbane, Australia. Several isolates fermented efficiently at laboratory scale, but failed to grow at industrial scale due to the combination of maltose and pressure stress. Systems biology showed that the synergistic metabolic defects caused by these dual stresses converged on amino acid nutrient uptake. Glucoamylase addition relieved maltose stress and allowed industrial scale fermentation using wild yeast. Our workflow allows efficient collection and characterisation of diverse wild yeast isolates, identification of interventions to allow their use at industrial scale, and investigation of the genetic and metabolic diversity of wild yeasts.
Cre-Lox miRNA-delivery technology optimized for inducible microRNA and gene-silencing studies in zebrafish
Authors: Guo Fangfei , Tromp Alisha , Wang Haitao , Hall Thomas E , Giacomotto Jean 
Published: February 2024

ABSTRACTWhile many genetic tools exist for zebrafish, this animal model is still lacking a robust gene-silencing and microRNA-delivery technology enabling spatio-temporal control and reliable traceability. We have recently demonstrated that the use of engineered pri-miR backbones can be used to both trigger stable and heritable gene knockdown and/or express microRNA(s) of choice in this organism. This approach/material fills a gap that exists in the zebrafish genetic toolbox to study microRNA biology and has the potential to be a powerful complementary tool to CRISPR-knockout and CRISPR-interference approaches by enabling conditional, traceable tissue-specific and polygenic gene-silencing. However, to date, this miRNA-expressing technology still presents important limitations. First, to trigger potent knockdown(s), multiple synthetic-miRNAs must be expressed simultaneously which compromises the co-expression of fluorescent marker(s) and knockdown traceability, thereby reducing the interest and versatility of this approach. Second, when the gene knockdown triggers significant phenotypes, like homozygous mutants with severe early phenotypes, it is difficult, if not impossible, to maintain adult transgenic carriers. Here, to solve these problems and provide a mature RNAi and microRNA-delivery technology for zebrafish research, we have generated and validated new RNAi reagents and an inducible delivery system based on the Cre/Lox technology. This new system allows the creation of asymptomatic/silent carriers, easing the production of embryos with potent knockdowns that can be traced and spatiotemporally controlled. Following this technological development, we demonstrate the utility of our approach by generating novel inducible models of spinal muscular atrophy (SMA) that open new avenues for studying the normal and pathogenic functions of the smn1 gene, as well as for establishing large-scale screens. Finally, and very importantly, the materials and techniques developed here will simplify research into microRNA biology, as well as conditions involving haploinsufficiency and multiple genes.
Heterozygosity for Crohn’s Disease Risk Allele ofATG16L1Protects against Bacterial Infection
Authors: Yao Xiaomin , Rudensky Eugene , Martin Patricia K. , Zwack Erin E. , He Zhengxiang , Furtado Glaucia C. , Lira Sérgio A. , Torres Victor J. , Shopsin Bo , Cadwell Ken 
Published: February 2024

AbstractThe T300A substitution in ATG16L1 associated with Crohn’s Disease impairs autophagy, yet up to 50% of humans are heterozygous for this allele. Here we demonstrate that heterozygosity for the analogous substitution in mice (Atg16L1T316A), but not homozygosity, protects against lethalSalmonella entericaTyphimurium infection. One copy ofAtg16L1T316Awas sufficient to enhance cytokine production through inflammasome activation, which was necessary for protection. In contrast, two copies ofAtg16L1T316Ainhibited the autophagy-related process of LC3-associated phagocytosis (LAP) and increased susceptibility. Macrophages from human donors heterozygous forATG16L1T300Adisplayed elevated inflammasome activation while homozygosity impaired LAP, similar to mice. These results clarify how the T300A substitution impacts ATG16L1 function and suggest it can be beneficial to heterozygous carriers, providing an explanation for its prevalence.One-Sentence SummaryHeterozygosity of Crohn’s diseases risk variantATG16L1 T300Aconfers protection against bacterial infections.
A comprehensive personal omics clinical interpreter based on genomic and transcriptomic profiles
Authors: Liu Yaqing , Chen Qingwang , Chen Qiaochu , Sang Leqing , Wang Yunjin , Shi Leming , Zheng Yuanting , Guo Li , Yu Ying 
Published: February 2024

AbstractAdvances in precision medicine rely on the accurate identification and analysis of molecular alterations for personalized diagnostic, prognostic, and therapeutic decision-making. A critical obstacle is the integration of heterogeneous interpretations of clinically actionable alterations from various knowledgebases. Here, we present the Personal Omics Interpreter (POI), a web-based application engineered to aggregate and interpret therapeutic options, including targeted, immunological, and chemotherapeutic agents, by leveraging personal genomic and transcriptomic profiles. POI employs the Precision Medicine Knowledgebase (PreMedKB), an updated harmonized resource we previously reported, to annotate the clinically actionable somatic variants. It further incorporates a predictive algorithm to broaden therapeutic options according to established gene-gene interactions and offers insights into phenotypic responses of chemotherapeutic agents through phasing germline diplotypes. Validated against three cohort datasets encompassing over 22,000 cancer patients, POI demonstrates consistently high matching rates (94.7 ∼ 95.6%) between patients and suggested therapies, highlighting its potential in supporting precision-driven informed treatment strategies.
Criterion placement threatens the construct validity of neural measures of consciousness
Authors: Fahrenfort Johannes J. , Johnson Philippa A. , Kloosterman Niels A. , Stein Timo , van Gaal Simon 
Published: February 2024

AbstractHow consciousness arises from brain activity has been a topic of intense scientific research for decades. But how does one identify the neural basis of something that is intrinsically personal and subjective? A hallmark approach has been to ask observers to judge stimuli as ‘seen’ (conscious) and ‘unseen’ (unconscious) and use post hoc sorting of neural measurements based these judgments. Unfortunately, cognitive and response biases are known to strongly affect how observers place their criterion for judging stimuli as ‘seen’ vs. ‘unseen’, thereby confounding neural measures of consciousness. Surprisingly however, the effect of conservative and liberal criterion placement on neural measures of unconscious and conscious processing has never been explicitly investigated. Here we use simulations and electrophysiological brain measurements to show that conservative criterion placement has an unintuitive consequence: rather than selectively providing a cautious estimate of conscious processing, it inflates effect sizes in neural measures of both conscious and unconscious processing, while liberal criterion placement does the reverse. After showing this in simulation, we performed decoding analyses on two electroencephalography studies that employ common subjective indicators of conscious awareness, in which we experimentally manipulated the response criterion. The results confirm that the predicted confounding effects of criterion placement on neural measures of unconscious and conscious processing occur in empirical data, while further showing that the most widely used subjective scale, the Perceptual Awareness Scale (PAS), does not guard against criterion confounds. Follow-up simulations explicate how the experimental context determines whether the relative confounding effect of criterion placement is larger in neural measures of either conscious or unconscious processing. We conclude that criterion placement threatens the construct validity of neural measures of conscious and unconscious processing.
Rapid, direct, and sequence-specific identification of RNA viruses in various crop plants using CRISPR/Cas13a
Authors: Hak Hagit , Ostendorp Steffen , Reza Anton , Ishgur Greenberg Shany , Pines Gur , Kehr Julia , Spiegelman Ziv 
Published: February 2024

SummaryPlant viruses are destructive pathogens causing significant damage to various crop species. Rapid, sensitive, and specific detection is crucial for the effective containment of emerging and resistance-breaking viruses. CRISPR/Cas has been established as a useful tool for plant virus identification. However, its application for on-site, direct detection of viruses from plant tissues is still limited. In this study, we present a rapid method for detecting viruses directly from RNA of different crop species using CRISPR/Cas13a. We successfully applied this method to identify tomato brown rugose fruit virus (ToBRFV) in infected tomato plants and differentiate it from closely related tobamoviruses. ToBRFV could be identified in a 100-fold dilution and early during infection, prior to the onset of viral symptoms. Moreover, CRISPR/Cas13a was used to directly identify cucumber green mottle mosaic virus (CGMMV) in cucumber plants and turnip mosaic virus (TuMV) inBrassica napusplants. Finally, we developed a user-friendly, extraction-free, 15-minute protocol for on-site ToBRFV identification using a portable fluorescent viewer and a mobile phone camera. This protocol was successfully applied for ToBRFV detection in a commercial greenhouse. These results demonstrate that CRISPR/Cas13a is a robust technology for direct, rapid, sensitive, and specific identification of multiple viruses in different crop plants that can be easily implemented for on-site detection.
Trends in genome diversity of small populations under a conservation program: a case study of two French chicken breeds
Authors: Bortoluzzi Chiara , Restoux Gwendal , Rouger Romuald , Desnoues Benoit , Petitjean Florence , Bosse Mirte , Tixier-Boichard Michèle 
Published: February 2024

AbstractLivestock biodiversity is declining globally at rates unprecedented in human history. Of all avian species, chickens are among the most affected ones because many local breeds have a small effective population size that makes them more susceptible to demographic and genetic stochasticity. The maintenance of genetic diversity and control over genetic drift and inbreeding by conservation programs are fundamental to ensure the long-term survival and adaptive potential of a breed. However, while the benefits of a conservation program are well understood, they are often overlooked. We here used temporal whole-genome sequencing data to assess the effects of a conservation program on the genetic diversity (Δπ), deleterious variation (ΔL), and inbreeding (ΔF) of two local French chicken breeds, the Barbezieux and Gasconne. We showed that when the conservation program is consistent over time and does not undergo any major organisational changes (i.e., Barbezieux), the loss of genetic diversity is limited. This was true for both pedigree and genomic inbreeding but also for the genetic load estimated from functionally important genome-wide variants. However, when a conservation program is interrupted or re-initiated from scratch (i.e., Gasconne), the loss of genetic diversity can hardly be limited as a result of the bottleneck effect associated with the re-sampling. Our results reinforce the imperative to establish and sustain existing conservation programs that aim to keep populations with a relatively small effective population size from the brink of extinction. Moreover, we conclude by encouraging the use of molecular data to more effectively monitor inbreeding at the genome level while improving fitness by tracking protein-coding and non-coding deleterious variants.