bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting subtle transcriptomic perturbations induced by lncRNAs Knock-Down in single-cell CRISPRi screening using a new sparse supervised autoencoder neural network
Authors: Truchi Marin , Lacoux Caroline , Gille Cyprien , Fassy Julien , Magnone Virginie , Lopez-Goncalvez Rafael , Girard-Riboulleau Cédric , Manosalva-Pena Iris , Gautier-Isola Marine , Lebrigand Kevin , Barbry Pascal , Spicuglia Salvatore , Vassaux Georges , Rezzonico Roger , Barlaud Michel , Mari Bernard 
Published: July 2023

AbstractSingle-cell CRISPR-based transcriptome screens are potent genetic tools for concomitantly assessing the expression profiles of cells targeted by a set of guides RNA (gRNA), and inferring target gene functions from the observed perturbations. However, due to various limitations, this approach lacks sensitivity in detecting weak perturbations and is essentially reliable when studying master regulators such as transcription factors. To overcome the challenge of detecting subtle gRNA induced transcriptomic perturbations and classifying the most responsive cells, we developed a new supervised autoencoder neural network method. Our Sparse supervised autoencoder (SSAE) neural network provides selection of both relevant features (genes) and actual perturbed cells. We applied this method on an in-house single-cell CRISPR-interference-based (CRISPRi) transcriptome screening (CROP-Seq) focusing on a subset of long non-coding RNAs (lncRNAs) regulated by hypoxia, a condition that promote tumor aggressiveness and drug resistance, in the context of lung adenocarcinoma (LUAD). The CROP-seq library of validated gRNA against a subset of lncRNAs and, as positive controls, HIF1A and HIF2A, the 2 main transcription factors of the hypoxic response, was transduced in A549 LUAD cells cultured in normoxia or exposed to hypoxic conditions during 3, 6 or 24 hours. We first validated the SSAE approach on HIF1A and HIF2 by confirming the specific effect of their knock-down during the temporal switch of the hypoxic response. Next, the SSAE method was able to detect stable short hypoxia-dependent transcriptomic signatures induced by the knock-down of some lncRNAs candidates, outperforming previously published machine learning approaches. This proof of concept demonstrates the relevance of the SSAE approach for deciphering weak perturbations in single-cell transcriptomic data readout as part of CRISPR-based screening.
The scorpionfly (Panorpa cognata) genome highlights conserved and derived features of the peculiar dipteran X chromosome
Authors: Lasne Clementine , Elkrewi Marwan , Toups Melissa A. , Layana Lorena , Macon Ariana , Vicoso Beatriz 
Published: July 2023

AbstractMany insects carry an ancient X chromosome - the Drosophila Muller element F - that likely predates their origin. Interestingly, the X has undergone turnover in multiple fly species (Diptera) after being conserved for more than 450 MY. The long evolutionary distance between Diptera and other sequenced insect clades makes it difficult to infer what could have contributed to this sudden increase in rate of turnover. Here, we produce the first genome and transcriptome of a long overlooked sister-order to Diptera: Mecoptera. We compare the scorpionflyPanorpa cognataX-chromosome gene content, expression, and structure, to that of several dipteran species as well as more distantly-related insect orders (Orthoptera and Blattodea). We find high conservation of gene content between the mecopteran X and the dipteran Muller F element, as well as several shared biological features, such as the presence of dosage compensation and a low amount of genetic diversity, consistent with a low recombination rate. However, the two homologous X chromosomes differ strikingly in their size and number of genes they carry. Our results therefore support a common ancestry of the mecopteran and ancestral dipteran X chromosomes, and suggest that Muller element F shrank in size and gene content after the split of Diptera and Mecoptera, which may have contributed to its turnover in dipteran insects.
Brain network interconnectivity dynamics explain metacognitive differences in listening behavior
Authors: Alavash Mohsen , Obleser Jonas 
Published: July 2023

AbstractComplex auditory scenes pose a challenge to attentive listening, rendering listeners slower and more uncertain in their perceptual decisions. How can we explain such behaviors from the dynamics of cortical networks that pertain to the control of listening behavior? We here follow up on the hypothesis that human adaptive perception in challenging listening situations is supported by modular reconfiguration of auditory-control networks in a sample of N=40 participants (13 males) who underwent resting-state and task functional magnetic resonance imaging (fMRI). Individual titration of a spatial selective auditory attention task maintained an average accuracy of∼ 70% but yielded considerable inter-individual differences in listeners’ response speed and reported confidence in their own perceptual decisions. Whole-brain network modularity increased from rest to task by reconfiguring auditory, cinguloopercular, and dorsal attention networks. Specifically, interconnectivity between the auditory network and cinguloopercular network decreased during the task relative to the resting state. Additionally, interconnectivity between the dorsal attention network and cinguloopercular network increased. These interconnectivity dynamics were predictive of individual differences in response confidence, the degree of which was more pronounced after incorrect judgments. Our findings uncover the behavioral relevance of functional crosstalk between auditory and attentional-control networks during metacognitive assessment of one’s own perception in challenging listening situations and suggest two functionally dissociable cortical networked systems that shape the considerable metacognitive differences between individuals in adaptive listening behavior.Significance StatementThe ability to communicate in challenging listening situations varies not only objectively between individuals but also in terms of their subjective perceptual confidence. Using fMRI and a challenging auditory task, we demonstrate that this variability in the metacognitive aspect of listening behavior is reflected on a cortical level through the modular reconfiguration of brain networks. Importantly, task-related modulation of interconnectivity between the cinguolopercular network and each auditory and dorsal attention network can explain for individuals’ differences in response confidence. This suggests two dissociable cortical networked systems that shape the individual evaluation of one’s own perception during listening, promising new opportunities to better understand and intervene in deficits of auditory perception such as age-related hearing loss or auditory hallucinations.
Experimental drought reduces the productivity and stability of a recovering calcareous grassland
Authors: Jackson J. , Middleton S.L , Lawson C. S. , Jardine E. , Hawes N. , Maseyk K. , Salguero-Gómez R , Hector A. 
Published: July 2023

AbstractGrasslands comprise 40% of terrestrial ecosystems and are globally important for food production, carbon storage, and other ecosystem services. However, grasslands in many areas are becoming increasingly exposed to extreme wet and dry periods resulting from global temperature increases.Therefore, understanding how grasslands will respond to climate change is a pressing issue for managing changes to biodiversity and ecosystem service provision.Here, we use experimental manipulations of precipitation (50% increase and 50% decrease of growing-season precipitation) to investigate the resistance of the diversity and productivity of a calcareous grassland community recovering from historical agricultural conversion.We found that decreasing growing season precipitation led to reductions of mean productivity (25 % decrease in peak above-ground biomass) and its temporal stability (54 % increase in biomass variance across years). However, the grassland community composition was resistant to the precipitation manipulations, with no clear difference in community compositional turnover, dissimilarity, or biodiversity indices. Furthermore, the precipitation manipulations had no effect on the path of ongoing (30 year) recovery of grassland plant diversity from the period of previous agricultural conversion.While the diversity of this calcareous grassland was resistant to precipitation extremes (at least in the short term), sustained reductions in growing-season precipitation reduced productivity and its temporal stability demonstrating that different properties of grasslands can vary in their responses to changes in precipitation.
A side-by-side comparison of peptide-delivered antisense antibiotics employing different nucleotide mimics
Authors: Ghosh Chandradhish , Popella Linda , Dhamodharan V. , Jung Jakob , Barquist Lars , Höbartner Claudia , Vogel Jörg 
Published: July 2023

ABSTRACTAntisense oligomer (ASO)-based antibiotics that target mRNAs of essential bacterial genes have great potential for counteracting antimicrobial resistance and for precision microbiome editing. To date, the development of such antisense antibiotics has primarily focused on using phosphorodiamidate morpholino (PMO) and peptide nucleic acid (PNA) backbones, largely ignoring the growing number of chemical modalities that have spurred the success of ASO-based human therapy. Here, we directly compare the activities of seven chemically distinct 10mer ASOs, all designed to target the essential geneacpPupon delivery with a KFF-peptide carrier intoSalmonella.Our systematic analysis of PNA, PMO, phosphorothioate-modified DNA (PTO), 2’-methylated RNA (RNA-OMe), 2’-methoxyethylated RNA (RNA-MOE), 2’-fluorinated RNA (RNA-F) and 2’-4’-locked RNA (LNA) is based on a variety ofin vitroandin vivomethods to evaluate ASO uptake, target pairing and inhibition of bacterial growth. Our data show that only PNA and PMO are efficiently delivered by the KFF peptide intoSalmonellato inhibit bacterial growth. Nevertheless, the strong target binding affinity andin vitrotranslational repression activity of LNA and RNA-MOE make them promising modalities for antisense antibiotics that will require the identification of an effective carrier.
Neural entrainment to speech in theta range is affected by language properties but not by the native language of the listeners
Authors: Özer Ege Ekin , Silva Pereira Silvana , Sebastian-Galles Nuria 
Published: July 2023

AbstractA universal speech rhythm around 5 Hz, corresponding to syllable beats, is captured by neural oscillations in the human brain. However, there is significant variability in syllabic complexity across languages: some languages allow only simple syllables, while some allow more variation (a variation related to linguistic rhythm). Behavioral evidence suggests that humans show different patterns of speech segmentation depending on the linguistic rhythm of their native language. Here, we tested if the entrainment of neural oscillations in the theta range (3–8 Hz) to sentences of languages representative of different linguistic rhythms depends on participants’ native language rhythm or rather reflects language-specific rhythmic properties. We recorded EEG in two groups of participants: native speakers of English (stress-timed, Experiment 1) and native speakers of Spanish (syllable-timed, Experiment 2). Both groups listened tosaltanajresynthesized sentences from English (stress-timed), Spanish (syllable-timed) and Japanese (mora-timed), a procedure that removes comprehension but keeps language-specific phonological properties. Phase locking value between sentence envelopes and EEG showed the same pattern regardless of participants’ native language: lowest for English, intermediate for Spanish, and highest for Japanese. Our results suggest that entrainment to speech in the theta frequency range is sensitive to differences in variation in syllabic complexity across languages.
Bacterial sepsis triggers stronger transcriptomic immune responses in larger primates
Authors: McMinds Ryan , Jiang Rays H.Y. , Adapa Swamy R. , Cornelius Ruhs Emily , Munds Rachel A. , Leiding Jennifer W. , Downs Cynthia J. , Martin Lynn B. 
Published: July 2023

AbstractEmpirical data relating body mass to immune defense against infections remain limited. Although the Metabolic Theory of Ecology predicts that larger organisms would have weaker immune responses, recent studies have suggested that the opposite may be true. These discoveries have led to the Safety Factor hypothesis, which proposes that larger organisms have evolved stronger immune defenses because they carry greater risks of exposure to pathogens and parasites. In this study, we simulated sepsis by exposing blood from nine primate species to a bacterial lipopolysaccharide (LPS), measured the relative expression of immune and other genes using RNAseq, and fit phylogenetic models to determine how gene expression was related to body mass. In contrast to non-immune-annotated genes, we discovered hypermetric scaling in the LPS-induced expression of innate immune genes, such that large primates had a disproportionately greater increase in gene expression of immune genes compared to small primates. Hypermetric immune gene expression appears to support the Safety Factor hypothesis, though this pattern may represent a balanced evolutionary mechanism to compensate for lower per-transcript immunological effectiveness. This study contributes to the growing body of immune allometry research, highlighting its importance in understanding the complex interplay between body size and immunity over evolutionary timescales.Author SummaryUnderstanding the relationship between an animal’s size and its ability to defend against disease can inform predictions about evolutionary tradeoffs and susceptibility to infection. Two major theories – the Metabolic Theory of Ecology (MTE) and the Safety Factor hypothesis – offer opposing views on how body size influences it immune defenses. In this study, we compared the immune gene expression of nine primate species to a simulated bacterial infection. We found that larger species mounted a stronger transcriptional immune response, consistent with either the Safety Factor hypothesis or an evolutionary pressure to compensate for and balance the effects expected in the context of the MTE.
Association of Genetic Ancestry with Molecular Tumor Profiles in Colorectal Cancer
Authors: Rhead Brooke , Hein David M. , Pouliot Yannick , Guinney Justin , De La Vega Francisco M. , Sanford Nina N. 
Published: July 2023

AbstractBackgroundPrior research on molecular correlates of disparities in incidence and outcomes of colorectal cancer (CRC) have typically used self-reported or observed categories of race and ethnicity, which can be missing or inaccurate. Furthermore, race and ethnicity do not always capture genetic similarity well, particularly in admixed populations. To overcome these limitations, we examined associations of CRC tumor molecular profiles using genetic ancestry.MethodsSequencing was performed with the Tempus xT NGS 648-gene panel and whole exome capture RNA-Seq for 8,454 CRC patients. Genetic ancestry proportions were estimated for five continental groups, Africa (AFR), Americas (AMR), East Asia (EAS), Europe (EUR), and South Asia (SAS), using ancestry informative markers. We assessed association of genetic ancestry proportions and genetic ancestry-imputed race and ethnicity categories with somatic mutations in relevant CRC genes and in expression profiles, including consensus molecular subtypes (CMS).ResultsIncreased AFR ancestry was associated with higher odds of somatic mutations inAPC,KRASandPIK3CAand lower odds ofBRAFmutations. Additionally, increased EAS ancestry was associated with lower odds of mutations inKRAS, EUR with higher odds inBRAF, and the Hispanic/Latino category with lower odds inBRAF. Greater AFR ancestry and the non-Hispanic Black category were associated with higher rates of CMS3, while patients in the Hispanic/Latino category had more indeterminate CMS.ConclusionsUse of genetic ancestry enables identification of molecular differences in CRC tumor mutation frequencies and gene expression that may underlie observed differences by race and ethnicity, and suggests that subtype classifications such as CMS may benefit from greater patient diversity.
Native dynamics and allosteric responses in PTP1B probed by high-resolution HDX-MS
Authors: Woods Virgil A. , Abzalimov Rinat R. , Keedy Daniel A. 
Published: July 2023

AbstractProtein tyrosine phosphatase 1B (PTP1B) is a validated therapeutic target for obesity, diabetes, and certain types of cancer. In particular, allosteric inhibitors hold potential for therapeutic use, but an incomplete understanding of conformational dynamics and allostery in this protein has hindered their development. Here, we interrogate solution dynamics and allosteric responses in PTP1B using high-resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), an emerging and powerful biophysical technique. Using HDX-MS, we obtain a detailed map of the solution dynamics of apo PTP1B, revealing several flexible loops interspersed among more constrained and rigid regions within the protein structure, as well as local regions that exchange faster than expected from their secondary structure and buriedness. We demonstrate that our HDX rate data obtained in solution adds value to predictions of dynamics derived from a pseudo-ensemble constructed from ∼200 crystal structures of PTP1B. Furthermore, we report HDX-MS maps for PTP1B with active-site vs. allosteric small-molecule inhibitors. These maps reveal distinct, dramatic, and widespread effects on protein dynamics relative to the apo form, including changes to dynamics in locations distal (>35 Å) from the respective ligand binding sites. These results help shed light on the allosteric nature of PTP1B and the surprisingly far-reaching consequences of inhibitor binding in this important protein. Overall, our work showcases the potential of HDX-MS for elucidating protein conformational dynamics and allosteric effects of small-molecule ligands, and highlights the potential of integrating HDX-MS alongside other complementary methods to guide the development of new therapeutics.
Marketing placebo effect on consumption of reduced-sugar labeled products
Authors: Huang Li , Song Xi , Liu Matthew Tingchi 
Published: July 2023

PurposeThe purpose of this study is to enhance the understanding of the marketing placebo effect (MPE) by proposing and empirically testing a model of antecedents and consequences of MPE for reduced-sugar labeled products in the food industry.Design/methodology/approachAn online survey was conducted on a sample of 409 consumers to collect data on their health consciousness, sugar-induced anxiety, self-congruity, fresh start mindset and MPE of reduced front-of-pack sugar labeling in food products. Structural equation modeling (SEM) was used to analyze the data and test the hypotheses.FindingsThe results highlight the sugar-induced anxiety as the most pronounced determinant for the proposed placebo effect. Health consciousness was observed to indirectly influence the MPE via mediators (sugar-induced anxiety and self-congruity). Furthermore, the supporting role of the fresh start mindset moderates the relationships between health consciousness, sugar-induced anxiety, self-congruity and the MPE.Research limitations/implicationsThis study is one of the few to investigate the moderating effects of having a fresh start mindset on the MPE of reduced-sugar labeled products. Moreover, the study contributes to the growing body of research on the indirect effects of health consciousness on consumer behavior, highlighting the important role of emotional (anxiety) and self-congruity factors in shaping the MPE toward reduced-sugar labeled products.Practical implicationsBy understanding the complex interplay between the variables of the antecedents and consequences of MPE for reduced-sugar labeled products, which engenders consumer attitude and belief about sugar intake, marketers and policymakers can develop more effective campaign strategies to promote such products and, consequently, a healthy diet and lifestyle.Originality/valueThis study is one of the few to investigate the moderating effects of the fresh start mindset on the MPE of reduced-sugar labeled products. Moreover, the study contributes to the growing body of research on the indirect effects of health consciousness on consumer behavior, highlighting the critical role emotional (i.e. anxiety) and cognitive (i.e. self-congruity) factors play in shaping the outcome of the MPE of reduced-sugar labeling in products.
Eating halal: a serial mediation model for the effect of religiosity on the intention to purchase halal-certified food
Authors: Loussaief Aida , Ying-Chao Lin Julia , Phuc Dang Huu , Bouslama Neji , Cheng Julian Ming-Sung 
Published: July 2023

PurposeThis research discloses the effect of religiosity on purchasing intention through serial-mediation paths in a halal-certified food context. Borrowing from the identity theory while supplemented by the theory of planned behaviour (TPB) and the knowledge–attitude–practice (KAP) theory, a 4-layered framework is developed to investigate such an issue.Design/methodology/approach264 questionnaires are collected in the field study conducted in Tunis, Tunisia. Quota sampling method is applied. Testing of the hypotheses is performed using partial least square analysis.FindingsThe findings reveal that religiosity affects the four mediators—awareness, trust, subjective norm and perceived behavioural control—which in turn affect attitude, and purchase intention towards halal-certified food is eventually aroused. These four serial-mediation paths are further proved to form the mechanisms.Research limitations/implicationsThe field study participants are limited to consumers in Tunis. Besides, a mechanism to collect the data from general public including lower educated consumers should be necessary.Originality/valueThis research is a pioneering work investigating the sequential intervening effect in the religiosity-intention relationship in halal-certified food. The authors provide unique and fruitful insights into this relatively untapped field for academia and firms.