bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-frequency quantitative ultrasound to assess the acoustic properties of engineered tissues in vitro
Authors: Sebastian Joseph A. , Strohm Eric M. , Chérin Emmanuel , Mirani Bahram , Démoré Christine , Kolios Michael C. , Simmons Craig A. 
Published: August 2022

AbstractAcoustic properties of biomaterials and engineered tissues reflect their structure and cellularity. High-frequency ultrasound (US) can non-invasively characterize and monitor these properties with sub-millimetre resolution. We present an approach to estimate the acoustic properties of cell-laden hydrogels that accounts for frequency-dependent effects of attenuation in coupling media, hydrogel thickness, and interfacial transmission/reflection coefficients of US waves, all of which can bias attenuation estimates. Cell-seeded fibrin hydrogel disks were raster-scanned using a 40 MHz US transducer. Thickness, speed of sound, acoustic impedance, and acoustic attenuation coefficients were determined from the difference in the time-of-flight and ratios of the magnitudes of US signals, interfacial transmission/reflection coefficients, and acoustic properties of the coupling media. With this approach, hydrogel thickness was accurately measured by US, with excellent agreement to confocal microscopy (r2 = 0.97). Accurate thickness measurement enabled acoustic property measurements that were independent of hydrogel thickness, despite up to 60% reduction in thickness due to cell-mediated contraction. Notably, acoustic attenuation coefficients increased with increasing cell concentration (p<0.001), reflecting hydrogel cellularity independent of contracted hydrogel thickness. This approach enables accurate measurement of the intrinsic acoustic properties of biomaterials and engineered tissues to provide new insights into their structure and cellularity.
Bacterial phylogenetic markers in lake sediments as evidence for historical hemp retting
Authors: Rull Valentí , Sacristán-Soriano Oriol , Sànchez-Melsió Alexandre , Borrego Carles M. , Vegas-Vilarrúbia Teresa 
Published: August 2022

AbstractDocumenting prehistoric and historical hemp retting for fiber extraction is important in the study of human uses of this iconic plant and its cultural implications. In paleoecology, hemp retting is usually inferred from indirect proxies, notably anomalously high percentages of Cannabis pollen in lake sediments, but some recent studies have also used specific molecular biomarkers (cannabinol, Cannabis DNA) as a more straightforward evidence. Here we provide direct evidence of hemp retting by identifying phylogenetic signatures (16S rRNA genes) from pectinolytic bacteria actually responsible for the fermentation process that separates the fiber from the stalk, namely Bacillus, Clostridium, Escherichia, Massilia, Methylobacterium, Pseusomonas, Rhizobium and Rhodobacter. These analyses have been performed in the sediments from an Iberian lake previously considered as an important hemp retting site during the last five centuries, on the basis of Cannabis pollen abundances. The good match between biomarker and pollen evidence, in the context of the recent historical development of hemp industry in Spain, can be useful to interpret paleoecological records from other similar lakes in the way toward a more regional view on the introduction, spreading, uses and associated cultural connotations of Cannabis in the Iberian Peninsula within European and Mediterranean contexts.
Identification and functional prediction of sugar beet circRNAs involved in drought responses
Authors: Zou Chun-Lei , Guo Zhiqiang , Zhao Shanshan , Chen Jishuai , Zhang Chunlai 
Published: August 2022

AbstractDrought is one of the most common abiotic constraints on the quality and productivity of crops on a global scale. Despite the rapidly updating information on circRNAs (circular RNAs), their roles in the anti-drought regulation of sugar beet are least understood. As a newly recognized class of non-coding RNAs, circRNAs exert crucial effects on miRNA (microRNA) functionality, as well as on transcriptional regulation. To clarify the mechanism of how circRNAs of sugar beet respond to drought stress, deep sequencing was employed to characterize these circRNAs in a genome-wide manner under drought treatment. Our results identify a total of 17 differentially expressed circRNAs. As revealed by the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology outcomes, circRNAs were found capable and involved in drought-responsive events. Utilizing the target genes exhibiting direct/indirect associations with drought resistance, we established a circRNA–miRNA–mRNA meshwork based on the circRNAs that were expressed differentially. The probable sponge functions of novel_circ_0000442 and novel_circ_0000443 were exerted by targeting ath-miR157d. This helped regulate the expression of relevant target genes, including BVRB_1 g004570, BVRB_1 g005450, and BVRB_1 g005790, that were involved in drought response. Apart from offering novel understandings of anti-drought mechanisms, our findings lay a basis for probing deeper into the intricate regulatory networks of sugar beet genes.
Optimal Cancer Evasion in a Dynamic Immune Microenvironment
Authors: George Jason T. , Levine Herbert 
Published: August 2022

AbstractThe failure of cancer treatments, including immunotherapy, continues to be a major obstacle in preventing durable remission. This failure often results from tumor evolution, both genotypic and phenotypic, away from sensitive cell states. Here, we propose a mathematical framework for studying the dynamics of adaptive immune evasion that tracks the number of tumor-associated antigens available for immune targeting. We solve for the unique optimal cancer evasion strategy using stochastic dynamic programming and demonstrate that this policy results in increased cancer evasion rates when compared to a passive, fixed strategy. Our foundational model relates the likelihood and temporal dynamics of cancer evasion to features of the immune microenvironment, where tumor immunogenicity reflects a balance between cancer adaptation and host recognition. In contrast with a passive strategy, optimally adaptive evaders navigating varying selective environments result in substantially heterogeneous post-escape tumor antigenicity, giving rise to immunogenically hot and cold tumors.
Characterization of network hierarchy reflects cell-state specificity in genome organization
Authors: Wang Jingyao , Xue Yue , He Yueying , Quan Hui , Zhang Jun , Gao Yi Qin 
Published: August 2022

AbstractDynamic chromatin structure acts as the regulator of transcription program in crucial processes including cancer and cell development, but a unified framework for characterizing chromatin structural evolution remains to be established. Here, we performed graph inferences on Hi-C datasets and derived the chromatin contact networks (CCNs). We discovered significant decreases in information transmission efficiencies in CCNs of colorectal cancer (CRC) and T-lineage acute lymphoblastic leukemia (T-ALL) compared to corresponding normal controls through graph statistics. Through network embedding in Poincaré disk, the hierarchy depths of CCNs from CRC and T-ALL patients were found to be significantly shallower compared to their normal controls. A reverse trend of CCN change was observed for the transition from embryo to differentiated primary tissues. During early embryo developments of both human and mouse, the hierarchy of embedded chromatin structure gradually establishes. Additionally, we found tissue-specific conservation of hierarchy order in normal CCNs, which was disturbed in tumor. Our findings uncover the cell-state related hierarchical characteristics in chromatin structure, which reveal chromatin loci that play important roles in stabilizing the cellular conditions.
Gemini calling! First occurrence of successful twinning in wild, endangered lion-tailed macaques Macaca silenus in the Anamalai hills of the Western Ghats, India
Authors: Dhawale Ashni Kumar , Sinha Anindya 
Published: August 2022

AbstractWe recorded the first occurrence of surviving twins in lion-tailed macaques Macaca silenus from the Anamalai hills of the Western Ghats, India. The Puthuthottam population of liontailed macaques has historically been restricted to a rainforest fragment measuring 92ha, situated adjacent to human settlements, however, direct interactions between macaques and humans have been observed only in the last ten years. The population now visit settlements at a rate of 0.52/ day, and exploits anthropogenic foods. We recorded two sets of twins from the Puthuthottam population within a six-month period. Two previous cases of twins have been observed in this population since 2000, however, in both cases the twins did not survive beyond a few weeks. We followed and opportunistically collected ad libitum behavioural data on both sets of twins for a year between March 2019 to March 2020. Both mothers carrying the twins used the ground substrate extensively, however the mother with the younger set of twins also used the canopy and other precarious substrates such as cable wires. Our report shows that twinning occurs in lion-tailed macaques and twins are able to survive successfully. This report also supports previous evidence that twinning may occur in higher frequencies as a direct response to provisioning, with the mothers’ behaviour contributing to the successful survival of both twins.
The effect of Omicron breakthrough infection and extended BNT162b2 booster dosing on neutralization breadth against SARS-CoV-2 variants of concern
Authors: Graham Carl , Lechmere Thomas , Rehman Aisha , Seow Jeffrey , Kurshan Ashwini , Huettner Isabella , Maguire Thomas J.A. , Tam Jerry , Cox Daniel , Ward Christopher , Racz Mariusz , Waters Anele , Mant Christine , Malim Michael H. , Fox Julie , Doores Katie J. 
Published: August 2022

AbstractCOVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT126b2 at a short (3-4 week) or extended interval (8-12 weeks) and following a third vaccination approximately 6-8 months later. We show that whilst an extended interval between the first two vaccinations can greatly increase the breadth of the immune response and generate a higher proportion of Spike reactive memory B cells, a third vaccination leads to similar levels between the two groups. Furthermore, we show that the third vaccine dose enhances neutralization activity against omicron lineage members BA.1, BA.2 and BA.4/BA.5 and this is further increased following breakthrough infection during the UK omicron wave. These findings are relevant for vaccination strategies in populations where COVID-19 vaccine coverage remains low.
Finding a Needle in a Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection
Authors: Soni Apurv , Herbert Carly , Pretz Caitlin , Stamegna Pamela , Filippaios Andreas , Shi Qiming , Suvarna Thejas , Harman Emma , Schrader Summer , Nowak Chris , Schramm Eric , Kheterpal Vik , Behar Stephanie , Tarrant Seanan , Ferranto Julia , Hafer Nathaniel , Robinson Matthew , Achenbach Chad , Murphy Robert L. , Manabe Yukari C. , Gibson Laura , Barton Bruce , O’Connor Laurel , Fahey Nisha , Orvek Elizabeth , Lazar Peter , Ayturk Didem , Wong Steven , Zai Adrian , Cashman Lisa , Rao Lokinendi V , Luzuriaga Katherine , Lemon Stephenie , Blodgett Allison , Trippe Elizabeth , Barcus Mary , Goldberg Brittany , Roth Kristian , Stenzel Timothy , Heetderks William , Broach John , McManus David 
Published: August 2022

AbstractBackgroundRapid antigen tests (Ag-RDT) for SARS-CoV-2 with Emergency Use Authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially.ObjectiveTo describe a novel study design to generate regulatory-quality data to evaluate serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.DesignProspective cohort study using a decentralized approach. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days.SettingParticipants throughout the mainland United States were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Ag-RDTs were completed at home, and molecular comparators were shipped to a central laboratory.ParticipantsIndividuals over 2 years old from across the U.S. with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study.MeasurementsEnrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported.Key ResultsA total of 7,361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide.LimitationsNew, complex workflows required significant operational and data team support. Conclusions: The digital site-less approach employed in the ‘Test Us At Home’ study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19, and can be adapted across research disciplines to optimize study enrollment and accessibility.
Multi-ancestry meta-analysis and fine-mapping in Alzheimer’s Disease
Authors: Lake Julie , Solsberg Caroline Warly , Kim Jonggeol Jeffrey , Acosta-Uribe Juliana , Makarious Mary B. , Li Zizheng , Levine Kristin , Heutink Peter , Alvarado Chelsea , Vitale Dan , Kang Sarang , Gim Jungsoo , Lee Kun Ho , Pina-Escudero Stefanie D. , Ferrucci Luigi , Singleton Andrew B. , Blauwendraat Cornelis , Nalls Mike A. , Yokoyama Jennifer S. , Leonard Hampton L. 
Published: August 2022

ABSTRACTGenome-wide association studies (GWAS) of Alzheimer’s disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published and de novo GWAS from European, East Asian, African American, and Caribbean Hispanic populations to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer’s disease to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci and globally assessed the heterogeneity of known risk factors across populations. Additionally, we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to Alzheimer’s disease risk.
Hypoxia Sensing in Resident Cardiac Macrophages Regulates the Arg1 Macrophage Lineage During Ischemic Heart Injury
Authors: Kadyrov Farid F. , Koenig Andrew L. , Amrute Junedh M. , Dun Hao , Li Wenjun , Weinheimer Carla J. , Nigro Jessica M. , Kovacs Attila , Bredemeyer Andrea L. , Lai Lulu , Kopecky Benjamin J. , Penna Vinay , Kreisel Daniel , Lavine Kory J. 
Published: August 2022

AbstractMyocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia reperfusion injury, monocytes enter the heart and differentiate into diverse subpopulations of macrophages. The mechanisms and dynamics of monocyte differentiation within this context are unknown. We investigated the role of macrophage hypoxia sensing on monocyte differentiation following reperfused myocardial infarction. We show that deletion ofHif1α, a hypoxia response transcription factor, in resident cardiac macrophages led to increased remodeling and overrepresentation of a macrophage subset marked by arginase 1 (Arg1) expression. Arg1+macrophages displayed an inflammatory gene signature and were predicted to represent an intermediate state within the monocyte differentiation cascade. Lineage tracing of Arg1+macrophages revealed the existence of a monocyte differentiation trajectory consisting of multiple transcriptionally distinct macrophage states. We further showed that deletion ofHif1αin resident cardiac macrophages resulted in arrested progression through this trajectory and accumulation of an inflammatory intermediate state marked by persistentArg1expression. Collectively, our findings unveil distinct trajectories of monocyte differentiation and identify hypoxia sensing as an important determinant of monocyte differentiation following myocardial infarction.
Proteostasis governs differential temperature sensitivity across embryonic cell types
Authors: Dorrity Michael W. , Saunders Lauren M. , Duran Madeleine , Srivatsan Sanjay R. , Ewing Brent , Queitsch Christine , Shendure Jay , Raible David W. , Kimelman David , Trapnell Cole 
Published: August 2022

AbstractThe genetic program of embryonic development is remarkably robust, but temperature stress can degrade its ability to generate animals with invariant anatomy. While the stereotyped, consistent phenotypes associated with environmental stress during vertebrate development suggest that some cell types are more sensitive to stress than others, the basis of this sensitivity is unknown. Here, we characterize hundreds of individual zebrafish embryos under temperature stress using whole-animal single cell RNA-seq to identify cell types and molecular programs within them that drive phenotypic variability. We find that temperature perturbs the normal proportions and gene expression programs of numerous cell types and also introduces asynchrony in their development. The notochord is particularly sensitive to temperature stress, which we show is due to a specialized cell type, sheath cells. Further analyses show that sheath cells accumulate misfolded protein at elevated temperature, leading to a cascading structural failure of the notochord and irreversible anatomic defects in the embryo. Our study demonstrates that whole-animal single cell RNA-seq can characterize mechanisms important for developmental robustness and pinpoint molecular programs within specific cell types that constitute key failure points.
The dietary fiber guar gum ameliorates experimental autoimmune encephalomyelitis via attenuated Th1 activation and differentiation
Authors: Fettig Naomi M , Robinson Hannah G , Allanach Jessica R , Davis Katherine M , Simister Rachel L , Wang Elsie J , Sharon Andrew J , Jiayu Ye , Popple Sarah J , Seo Jung Hee , Gibson Deanna L , Crowe Sean A , Horwitz Marc S , Osborne Lisa C 
Published: August 2022

SummaryDietary fibers are potent modulators of immune responses that can restrain inflammation in multiple disease contexts. However, dietary fibers encompass a biochemically diverse family of carbohydrates, and it remains unknown how different fiber sources influence immunity. In a head-to-head comparison of four different high-fiber diets, we demonstrate a unique and potent ability of guar gum to reduce neuroinflammation in experimental autoimmune encephalomyelitis (EAE), a T cell-mediated mouse model of multiple sclerosis. CD4+ T cells from guar gum-fed mice have blunted Th1-skewing, reduced migratory capacity, and limited activation and proliferative capabilities. These changes are not explained by guar gum-specific alterations to the microbiota at the 16S rRNA level, nor by specific alterations in short chain fatty acids. These findings demonstrate specificity in the host response to fiber sources, and define a new pathway of fiber-induced CD4+ T cell immunomodulation that protects against pathologic neuroinflammation.
Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells
Authors: Gumuskaya Gizem , Srivastava Pranjal , Cooper Ben G. , Lesser Hannah , Semegran Ben , Garnier Simon , Levin Michael 
Published: August 2022

AbstractFundamental knowledge gaps exist with respect to the plasticity of cells from adult soma and the potential diversity of body shape and behavior in living constructs derived from such genetically wild-type cells. Here we introduce Anthrobots, a spheroid-shaped multicellular biological robot (biobot) platform with diameters ranging from 30 to 500 microns. Anthrobots have an inherent capacity for motility in aqueous environments, via cilia covering their surface. Each Anthrobot starts out as a single cell, derived from the adult human lung, and self-constructs into a multicellular motile biobot after having been cultured in extra cellular matrix for 2 weeks and transferred into a minimally viscous habitat. Anthrobots exhibit a wide range of behaviors with motility patterns ranging from tight loops to straight lines and speeds ranging from 5-50 microns/second. Our anatomical investigations reveal that this behavioral diversity is significantly correlated with their morphological diversity. Anthrobots can assume diverse morphologies from fully polarized to wholly ciliated bodies with spherical or ellipsoidal shapes, each correlating with a distinct movement type. Remarkably, as a function of these different movement types, Anthrobots were found to be capable of traversing live human tissues in various ways. Furthermore, Anthrobots were able to induce rapid repair of wounds in human neural cell sheets in vitro. By controlling microenvironmental cues in bulk, entirely novel structure, behavior, and biomedically-relevant capabilities can be discovered in morphogenetic processes without direct genetic editing or manual sculpting.Significance StatementWe demonstrate that normal, non-genetically-modified human tracheal cells can be induced to form a new proto-organism - Anthrobots - which exhibit spontaneous behavior, swimming around in one of several patterns, demonstrating plasticity for novel form and function inherent in even elderly human somatic cells. Moreover, Anthrobots are able to traverse over cultured neurons, settling down and causing repair under them: the nerves knit together across the wound gap due to the presence of the Anthrobot. A patient’s own cells can be harnessed to make a motile biological robot that can traverse human tissue and induce repair. In the future, this platform can deliver pro-regenerative therapeutics for a range of biomedical applications that will not trigger rejection or require immune suppression.