bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventing plasmid multimer formation in commonly used synthetic biology plasmids
Authors: Vaisbourd Elizabeth , Bren Anat , Alon Uri , Glass David S. 
Published: July 2024

AbstractPlasmids are an essential tool for basic research and biotechnology applications. To optimize plasmid-based circuits, it is crucial to control plasmid integrity, including the formation of plasmid multimers. Multimers are tandem repeats of entire plasmids formed during replication by failed dimer resolution. Multimers can affect the behavior of synthetic circuits, especially ones that include DNA-editing enzymes. However, occurrence of multimers is not commonly assayed. Here we survey four commonly used plasmid backbones for occurrence of multimers in cloning (JM109) and wild-type (MG1655) strains. We find that multimers occur appreciably only in MG1655, with the fraction of plasmids existing as multimers increasing with both plasmid copy number and culture passaging. In contrast, introduction of multimers into JM109 can produce strains containing only multimers. We present an MG1655ΔrecAsingle-locus knockout that avoids multimer production. These results can aid synthetic biologists in improving design and reliability of plasmid-based circuits.
Cell-Surface RNA Associates with Heparan Sulfate and RNA-Binding Proteins to Modulate Receptor-Ligand Interactions
Authors: Li Zeshi , Joshi Bhagyashree S. , Wijdeven Ruud H. , Santos-Barriopedro Irene , Shademan Milad , Bos Eric , Tanenbaum Marvin , Boons Geert-Jan , Sharp Thomas , Vermeulen Michiel , Raz Vered , Joo Chirlmin 
Published: July 2024

AbstractRecent discoveries have shown the presence of RNA molecules on the cell surface, defying the traditional view that RNA only functions intracellularly. However, it is not well understood how cell-surface RNA (csRNA) is stably present on the plasma membrane and what functions it performs on the cell surface. By exploiting the RNA-sensing ability of TLR7 as a specific recombinant probe to detect csRNA and coupling it with a genome-wide CRISPR-Cas9-knockout screening to identify genes essential for csRNA presentation on cells, we identified heparan sulfate (HS) as a crucial factor for RNA presentation on cells. Using the TLR7 binding probe, cell surface proximity labelling revealed that csRNA associates mechanistically with a plethora of RNA-binding proteins, and these interactions are crucial for csRNA presentation. Moreover, csRNA modulates receptor-ligand interactions between poliovirus receptor (PVR) and killer cell immunoglobulin-like receptor 2DL5 (KIR2DL5) by acting as a co-binder, recruiting the latter to cell surface. We provide a mechanistic understanding of csRNA presentation and unveil a new layer of complexity in the csRNA-dictated regulation of cell surface receptor-ligand interactions.
Two new species ofMylochromisspecies (Cichlidae) from Lake Malawi, Africa
Authors: Turner George F. 
Published: July 2024

AbstractTwo new species ofMylochromisRegan 1920 are described from specimens collected on shallow rocky habitats on the northwestern coast of Lake Malawi. The generic designation is based on their prominent oblique striped pattern and lack of any of the unique features of other Malawi cichlid genera with this pattern.Mylochromis rotundussp. nov. is distinguished from most congeneric species by its relatively deep, rounded body and lack of enlarged pharyngeal teeth. It is further distinguished fromM. semipalatusandM. melanonotus(if they are different species) by its relatively shorter snout.Mylochromis durophagussp. nov. is distinguished from most congeneric species by its strongly molarised pharyngeal dentition. It differs fromMylochromis molain having a shorter snout, less acutely pointed head profile, deeper body and in having a more continuous oblique stripe.Mylochromis durophagushas a much less steep head profile thanMylochromis anaphyrmusorMylochromis sphaerodon. It is suggested thatMylochromis rotunduswas previously identified informally asMylochromis sp. ‘mollis north’, andM. durophagusasM. sp. ‘mollis chitande’. Lectotypes are designated for comparator speciesMylochromis sphaerodonandMylochromis subocularis.
Genetic Architecture and Analysis Practices of Circulating Metabolites in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program
Authors: Wang Nannan , Ockerman Franklin P. , Zhou Laura Y. , Grove Megan L. , Alkis Taryn , Barnard John , Bowler Russell P. , Clish Clary B. , Chung Shinhye , Drzymalla Emily , Evans Anne M. , Franceschini Nora , Gerszten Robert E. , Gillman Madeline G. , Hutton Scott R. , Kelly Rachel S. , Kooperberg Charles , Larson Martin G. , Lasky-Su Jessica , Meyers Deborah A. , Woodruff Prescott G. , Reiner Alexander P. , Rich Stephen S. , Rotter Jerome I. , Silverman Edwin K. , Ramachandran Vasan S. , Weiss Scott T. , Wong Kari E. , Wood Alexis C. , Wu Lang ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Yarden Ronit , Blackwell Thomas W. , Smith Albert V. , Chen Han , Raffield Laura M. , Yu Bing 
Published: July 2024

AbstractCirculating metabolite levels partly reflect the state of human health and diseases and can be impacted by genetic determinants. Hundreds of loci associated with circulating metabolites have been identified; however, most findings focus on predominantly European ancestry or single-study analyses. Leveraging the rich metabolomics resources generated by the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program, we harmonized and accessibly cataloged 1,729 circulating metabolites among 25,058 ancestrally diverse samples. We provided a set of reasonable strategies for outlier and imputation handling to process metabolite data. Following the practical analysis framework, we further performed a genome-wide association analysis on 1,135 selected metabolites using whole genome sequencing data from 16,359 individuals passing the quality control filters, and discovered 1,778 independent loci associated with 667 metabolites. Among 108 novel locus-metabolite pairs, we detected not only novel loci within previously implicated metabolite associated genes but also novel genes (such asGAB3andVSIG4located in the X chromosome) that have putative roles in metabolic regulation. In the sex-stratified analysis, we revealed 85 independent locus-metabolite pairs with evidence of sexual dimorphism, including well-known metabolic genes such asFADS2,D2HGDH,SUGP1,UTG2B17, strongly supporting the importance of exploring sex difference in the human metabolome. Taken together, our study depicted the genetic contribution to circulating metabolite levels, providing additional insight into the understanding of human health.
An ultraconserved snoRNA-like element in long noncoding RNACRNDEpromotes ribosome biogenesis and cell proliferation
Authors: Lee Jong-Sun , Dan Tu , Zhang He , Cheng Yujing , Rehfeld Frederick , Brugarolas James , Mendell Joshua T. 
Published: July 2024

ABSTRACTCancer cells frequently upregulate ribosome production to support tumorigenesis. While small nucleolar RNAs (snoRNAs) are critical for ribosome biogenesis, the roles of other classes of noncoding RNAs in this process remain largely unknown. Here we performed CRISPRi screens to identify essential long noncoding RNAs (lncRNAs) in renal cell carcinoma (RCC) cells. This revealed that an alternatively-spliced isoform of lncRNAColorectal Neoplasia Differentially Expressedcontaining an ultraconserved element (UCE), referred to asCRNDEUCE, is required for RCC cell proliferation.CRNDEUCElocalizes to the nucleolus and promotes 60S ribosomal subunit biogenesis. The UCE ofCRNDEfunctions as an unprocessed C/D box snoRNA that directly interacts with ribosomal RNA precursors. This facilitates delivery of eIF6, a key 60S biogenesis factor, which binds toCRNDEUCEthrough a sequence element adjacent to the UCE. These findings highlight the functional versatility of snoRNA sequences and expand the known mechanisms through which noncoding RNAs orchestrate ribosome biogenesis.
Diet of Andean leaf-eared mice (Phyllotis) living at extreme elevations on Atacama volcanoes: insights from metagenomics, DNA metabarcoding, and stable isotopes
Authors: Quezada-Romegialli Claudio , Quiroga-Carmona Marcial , D’Elía Guillermo , Harrod Chris , Storz Jay F. 
Published: July 2024

AbstractOn the flanks of >6000 m Andean volcanoes that tower over the Atacama Desert, leaf-eared mice (Phyllotis vaccarum) live at extreme elevations that surpass known vegetation limits. What the mice eat in these barren, hyperarid environments has been the subject of much speculation. According to the arthropod fallout hypothesis, sustenance is provided by windblown insects that accumulate in snowdrifts (‘aolian deposits’). It is also possible that mice feed on saxicolous lichen or forms of cryptic vegetation that have yet to be discovered at such high elevations. We tested hypotheses about the diet of mice living at extreme elevations on Atacama volcanoes by combining metagenomic and DNA metabarcoding analyses of gut contents with stable-isotope analyses of mouse tissues. Genomic analyses of contents of the gastrointestinal tract of a live-captured mouse from the 6739 m summit of Volcán Llullaillaco revealed evidence for an opportunistic but purely herbivorous diet, including lichens. Although we found no evidence of animal DNA in gut contents of the summit mouse, stable isotope data indicate that mice native to elevations at or near vegetation limits (∼5100 m) include a larger fraction of animal prey in their diet than mice from lower elevations. Some plant species detected in the gut contents of the summit mouse are known to exist at lower elevations at the base of the volcano and in the surrounding Altiplano, suggesting that such plants may occur at higher elevations beneath the snowpack or in other cryptic microhabitats.
“They don’t know how to live with a child with these conditions, they can’t understand…”: The lived experiences of parenting a child with a genetic neurodevelopmental disorder
Authors: Low Karen J. , Treneman-Evans Georgia , Wynn Sarah L ,   GenROC Study Consortium, Ingram Jenny 
Published: July 2024

AbstractBackgroundA genetic neurodevelopmental diagnosis (GND) impacts all aspects of a child and family’s life. GNDs are rare; most have limited natural history data. We aimed to understand parents’ experiences around data acquisition about their child’s GNDs which can help inform clinical practice.Design and participantsThis analysis is part of the UK multicentre GenROC study. We conducted 17 semi-structured interviews with parents of children with GNDs (aged 0-15 years). Data were analysed following the principles of thematic analysis.ResultsFive main themes are reported:Impact on the family around a genetic diagnosisDistress results from diagnosis wait, the act of receiving it, associated irreversibility (loss of hope) and family/reproductive implications.GNDs and Uncertainty: Lack of data and rareness causes uncertainty for the future.Relationships with health professionalsPositive where parents are empowered and feel part of the team; Negative –parents feel not heard/believed or lack of expertise/understanding.Parent mental healthGNDs can be a significant burden to family life. Need for advocating for services is a negative impact. Isolation through rareness is a factor – this can be helped by support networks which mostly consist of gene specific Facebook groups.Development of positive parent identitiesincluding that of advocate, professional and educator.ConclusionsGNDs represent a major challenge for families, clinicians and service providers. Distressed parents are struggling to cope with challenges and suffer poor mental health. Psychosocial support, better signposting, and health professional education may help.Patient contributionPPI group contributed to topic guide development and commented on findings.
Instability of high polygenic risk classification and mitigation by integrative scoring
Authors: Misra Anika , Truong Buu , Urbut Sarah M. , Sui Yang , Fahed Akl C. , Smoller Jordan W. , Patel Aniruddh P. , Natarajan Pradeep 
Published: July 2024

AbstractPolygenic risk scores (PRS) continue to improve with novel methods and expanding genome-wide association studies. Healthcare and commercial laboratories are increasingly deploying PRS reports to patients, but it is unknown how the classification of high polygenic risk changes across individual PRS. Here, we assessed association and classification performance of cataloged PRS for three complex traits. We chronologically ordered all trait-related publications (Pubn) and identified the single PRS Best(Pubn) for each Pubnthat had the strongest association with the target outcome. While each Best(Pubn) demonstrated generally consistent population-level strengths of associations, classification of individuals in the top 10% of each Best(Pubn) distribution varied widely. Using the PRSmix framework, which integrates information across several PRS to improve prediction, we generate corresponding ChronoAdd(Pubn) scores for each Pubnthat combine all polygenic scores from all publications up to and including Pubn. When compared with Best(Pubn), ChronoAdd(Pubn) scores demonstrated more consistent high-risk classification amongst themselves. This integrative scoring approach provides stable and reliable classification of high-risk individuals, and is an adaptable framework into which new scores can be incorporated as they are introduced, integrating easily with current PRS implementation strategies.
TORC1-dependent control of fission yeast cohesin
Authors: Besson Dorian , Vaur Sabine , Vazquez Stéphanie , Tournier Sylvie , Gachet Yannick , Birot Adrien , Claverol Stéphane , Marston Adèle , Damdimopoulos Anastasios , Ekwall Karl , Javerzat Jean-Paul 
Published: July 2024

ABSTRACTThe Target of Rapamycin Complex 1 (TORC1) integrates cellular cues and adapts cell growth and metabolism through substrate-specific phosphorylation. A genetic screen for suppressors of a conditional mutant of the cohesin loader Mis4 identified hypomorphic mutants of TORC1. Downregulation of TORC1 enhanced the binding of cohesin and its loader to their regular sites on chromosomes. In the context of impaired cohesin loading, TORC1 downregulation rescued chromosome segregation whereas upregulation had the opposite effect, suggesting environmental cues impinge on the robustness of chromosome segregation. TORC1 co-purified with cohesin from cellular extracts and the phosphorylation level of specific residues on Mis4 and cohesin were reduced in TORC1 mutants. Cohesin mutations mimicking the non-phosphorylated state mirrored the effects of TORC1 downregulation. Challenging cells with various conditions revealed that Mis4 and TORC1 regulate a common set of genes involved in the response to environmental changes. These genes are preferentially located far from centromeres and close to telomeres. We propose that cohesin is an effector of TORC1, orchestrating alterations in chromosome structure that facilitate cellular adaptation to environmental changes.
Defensive symbiont genotype distributions are linked to parasitoid attack networks
Authors: Wu Taoping , Rodrigues Anoushka A. , Fayle Tom , Henry Lee M. 
Published: July 2024

ABSTRACTFacultative symbionts are widespread in arthropods and can provide important services such as protection from natural enemies. Yet what shapes associations with defensive symbionts in nature remains unclear. Two hypotheses suggest that either interactions with antagonists, or host plants, may explain the prevalence of symbionts through shared selective pressures and routes of horizontal transmission. Here we investigate the factors driving similarities in theHamiltonella defensasymbiosis shared among host species within field collected aphid communities. We show that,Hamiltonella’sgenotype distribution strongly aligns with sharing the same parasitoids, rather than host plants, highlighting parasitoids as a key selective agent shaping the symbiosis across host species. Our data indicates parasitoid host-specificity drives the prevalence of specific aphid-Hamiltonellaassociations, suggesting defensive symbioses are maintained by the selective pressure imposed by dominant parasitoid species. These findings underscore the importance of interactions with natural enemies in explaining patterns of defensive symbiosis in nature.
CRISPR-inhibition screen for lncRNAs linked to melanoma growth and metastasis
Authors: Petroulia Stavroula , Hockemeyer Kathryn , Tiwari Shashank , Berico Pietro , Shamloo Sama , Banijamali Seyedeh Elnaz , Vega-Saenz de Miera Eleazar , Gong Yixiao , Thandapani Palaniraja , Wang Eric , Schulz Michael , Tsirigos Aristotelis , Osman Iman , Aifantis Ioannis , Imig Jochen 
Published: July 2024

AbstractMelanoma being one of the most common and deadliest skin cancers, has been rising since the past decade. Patients at advanced stages of the disease have very poor prognoses, as opposed to at the earlier stages. Nowadays the standard-of-care of advanced melanoma is resection followed by immune checkpoint inhibition based immunotherapy. However, a substantial proportion of patients either do not respond or develop resistances. This underscores a need for novel approaches and therapeutic targets as well as a better understanding of the mechanisms of melanoma pathogenesis. Long non-coding RNAs (lncRNAs) comprise a poorly characterized class of functional players and promising targets in promoting malignancy. Certain lncRNAs have been identified to play integral roles in melanoma progression and drug resistances, however systematic screens to uncover novel functional lncRNAs are scarce. Here, we profile differentially expressed lncRNAs in patient derived short-term metastatic cultures and BRAF-MEK-inhibition resistant cells. We conduct a focused growth-related CRISPR-inhibition screen of overexpressed lncRNAs, validate and functionally characterize lncRNA hits with respect to cellular growth, invasive capacities and apoptosis in vitro as well as the transcriptomic impact of our lead candidate the novel lncRNA XLOC_030781. In sum, we extend the current knowledge of ncRNAs and their potential relevance on melanoma.SignificancePreviously considered as transcriptional noise, lncRNAs have emerged as novel players in regulating many cellular aspects in health and disease including melanoma. However, the number and as well as the extent of functional significance of most lncRNAs remains elusive. We provide a comprehensive strategy to identify functionally relevant lncRNAs in melanoma by combining expression profiling with CRISPR-inhibition growths screens lowering the experimental effort. We also provide a larger resource of differentially expressed lncRNAs with potential implications in melanoma growth and invasion. Our results broaden the characterized of lncRNAs as potential targets for future therapeutic applications.
Neural correlates of phonetic categorization under auditory (phoneme) and visual (grapheme) modalities
Authors: Bidelman Gavin M. , York Ashleigh , Pearson Claire 
Published: July 2024

AbstractWe tested whether the neural mechanisms of phonetic categorization are specific to speech sounds or generalize to graphemes (i.e., visual letters) of the same phonetic label. Given that linguistic experience shapes categorical processing, and letter-speech sound matching plays a crucial role during early reading acquisition, we hypothesized sound phoneme and visual grapheme tokens representing the same linguistic identity might recruit common neural substrates, despite originating from different sensory modalities. Behavioral and neuroelectric brain responses (ERPs) were acquired as participants categorized stimuli from sound (phoneme) and homologous letter (grapheme) continua each spanning a /da/ - /ga/ gradient. Behaviorally, listeners were faster and showed stronger categorization of phoneme compared to graphemes. At the neural level, multidimensional scaling of the EEG revealed responses self-organized in a categorial fashion such that tokens clustered within their respective modality beginning ∼150-250 ms after stimulus onset. Source-resolved ERPs further revealed modality-specific and overlapping brain regions supporting phonetic categorization. Left inferior frontal gyrus and auditory cortex showed stronger responses for sound category members compared to phonetically ambiguous tokens, whereas early visual cortices paralleled this categorical organization for graphemes. Auditory and visual categorization also recruited common visual association areas in extrastriate cortex but in opposite hemispheres (auditory = left; visual=right). Our findings reveal both auditory and visual sensory cortex supports categorical organization for phonetic labels within their respective modalities. However, a partial overlap in phoneme and grapheme processing among occipital brain areas implies the presence of an isomorphic, domain-general mapping for phonetic categories in dorsal visual system.
“Coolness” and “joy” in games: factors influencing mobile game players' willingness to make in-game purchases
Authors: Ma Yining , He Wang 
Published: July 2024

PurposeThis study aims to deeply explore the factors influencing mobile game players' willingness to make in-game purchases, providing references for game developers and marketers to formulate effective strategies.Design/methodology/approachThis research integrates the coolness factors and hedonic motivation system acceptance model to construct a comprehensive theoretical model analyzing mobile game players' willingness to make in-game purchases. The framework includes multidimensional variables such as joy, coolness, immersion, and game experience. Using data from 392 surveys collected from mobile game forums and social networks, the study employs structural equation modeling to analyze the factors and mechanisms influencing players' willingness to make in-game purchases and to verify the related research hypotheses.FindingsThe findings reveal that coolness factors have a significant positive impact on game experience and immersion, which in turn affect players' willingness to make in-game purchases. Game experience has a significant positive impact on both immersion and purchase willingness. A good game experience not only increases players' immersion but also directly enhances their willingness to make in-game purchases. Immersion plays a mediating role in the influence of coolness factors and joy on purchase willingness.Originality/valueBy integrating coolness theory with the hedonic motivation system acceptance model, this study constructs a comprehensive model to explore mobile game players' willingness to make in-game purchases. The combination of variables, including personal psychological and social psychological factors, provides a thorough analysis of the factors influencing mobile game purchase willingness, enriching existing research.
Design phase collaborative risk management factors: a case study of a green rating system in South Africa
Authors: Ojiako Udechukwu , Maseko Lungie , Root David , Venkatachalam Senthilkumar , Marshall Alasdair , Jasim Hussain AlRaeesi Eman , Chipulu Maxwell 
Published: July 2024

PurposeWe explore the design risk factors and associated managerial practices driving collaborative risk management for design efficacy in green building projects. By illuminating project design risk as an important project risk category in its own right, the study contributes to our understanding of optimising design efficacies for collaborative project risk management.Design/methodology/approachThe study comprises exploratory interviews conducted with 27 industry project practitioners involved in the design and delivery/implementation of Green Star-certified building projects in South Africa.FindingsThe findings discursively highlight seven sources of design risk. We also identify seven specific collaborative risk management practices for design efficacy emerging from a consideration of how risk environments vary in the Green Star-certified projects, each with its own project design risk implications.Originality/valueThe study advances our understanding of how collaborations emerging from particular relational yet context-specific practices can be optimised to strengthen project risk management.