bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and enhance immunity
Authors: Shmeleva Evgeniya V. , de Agüero Mercedes Gomez , Wagner Josef , Enright Anton J. , Macpherson Andrew J. , Ferguson Brian J. , Smith Geoffrey L. 
Published: July 2021

AbstractInteractions between pathogens, host microbiota and the immune system influence many physiological and pathological processes. In the 20th century, widespread dermal vaccination with vaccinia virus (VACV) led to the eradication of smallpox but how VACV interacts with the microbiota and whether this influences the efficacy of vaccination are largely unknown. Here we report that intradermal vaccination with VACV induces a large increase in the number of commensal bacteria in infected tissue, which enhance recruitment of inflammatory cells, promote tissue damage and increase immunity. Treatment of vaccinated specific-pathogen-free (SPF) mice with antibiotic, or infection of genetically-matched germ-free (GF) animals caused smaller lesions without alteration in virus titre. Tissue damage correlated with enhanced neutrophil and T cell infiltration and levels of pro-inflammatory tissue cytokines and chemokines. One month after vaccination, GF mice had reduced VACV-neutralising antibodies compared to SPF mice; while numbers of VACV-specific CD8+ T cells were equal in all groups of animals. Thus, skin microbiota may provide an adjuvant-like stimulus during vaccination with VACV. This observation has implications for dermal vaccination with live vaccines.Author SummarySmallpox was caused by variola virus and was eradicated by widespread dermal vaccination with vaccinia virus (VACV), a related orthopoxvirus of unknown origin. Eradication was declared in 1980 without an understanding of the immunological correlates of protection, or knowledge of the effect of smallpox vaccination on the local microbiota. Here we demonstrate that intradermal infection of mice with VACV induces a ∼1000-fold expansion of commensal skin bacteria that influence the recruitment of inflammatory cells into the infected tissue and enhance the size of the vaccination lesion. Antibiotic treatment reduced lesion size without changing virus titres. The bacterial expansion also contributes to the level of neutralizing antibodies at one month post vaccination, because genetically matched germ-free mice developed lower neutralizing antibodies than specific pathogen free controls. Thus, dermal infection by VACV enhanced bacterial growth and these bacteria promote pathology and enhance the antibody response. This finding has implication for dermal vaccination with live vaccines.
Localization of infection in neonatal rhesus macaques after oral viral challenge
Authors: Taylor Roslyn A. , McRaven Michael D. , Carias Ann M. , Anderson Meegan R. , Matias Edgar , Araínga Mariluz , Allen Edward J. , Rogers Kenneth A. , Gupta Sandeep , Kulkarni Viraj , Lakhashe Samir , Lorenzo-Redondo Ramon , Thomas Yanique , Strickland Amanda , Villinger Francois J , Ruprecht Ruth M. , Hope Thomas J. 
Published: July 2021

AbstractWhile vertical transmission of human immunodeficiency virus (HIV) can occur in utero and during delivery and through breastfeeding. We utilized Positron Emission Tomography (PET) imaging coupled with fluorescent microscopy of 64Cu-labeled photoactivatable-GFP-HIV (PA-GFP-BaL) to determine how HIV virions distribute and localize in neonatal rhesus macaques two and four hours after oral viral challenge. Our results show that by four hours after oral viral exposure, HIV virions localize to and penetrate the rectal mucosa. We also used a dual viral challenge with a non-replicative viral vector and a replication competent SHIV-1157ipd3N4 to examine viral transduction and dissemination at 96 hours. Our data show that while SHIV-1157ipd3N4 infection can be found in the oral cavity and upper gastrointestinal (GI) tract, the small and large intestine contained the largest number of infected cells. Moreover, we found that T cells were the biggest population of infected immune cells. Thus, thanks to these novel technologies, we are able to visualize and delineate of viral distribution and infection throughout the entire neonatal GI tract during acute viral infection.Author SummaryApproximately 1.8 million children are currently living with human immunodeficiency virus (HIV). While mother-to-child HIV transmission can occur in utero and during delivery, it most commonly occurs through breastfeeding, creating the need to understand how the virus moves throughout the body and infects the infant once breast milk is consumed. Here, we used multiple imaging techniques and PCR to determine how HIV distributes throughout the gastrointestinal tract after oral viral exposure and in which tissues and cell types become acutely infected. We found that HIV rapidly spreads throughout and penetrates the entire gastrointestinal tract as early as four hours after exposure. We also found that the intestine contained the largest number of infected cells at 96 hours and that most cells infected were T cells. Our study shows that these imaging technologies allow for the examination of viral distribution and infection in a rhesus macaque model.
Quantitative Single-Molecule Imaging with Statistical Machine Learning
Authors: Boonkird Artittaya , Nino Daniel F. , Milstein Joshua N. 
Published: July 2021

AbstractSingle-molecule localization microscopy (SMLM) is a super-resolution technique capable of rendering nanometer scale images of cellular structures. Recently, much effort has gone into developing SMLM into a quantitative method capable of determining the abundance and stoichiometry of macromolecular complexes. These methods often require knowledge of the complex photophysical properties of photoswitchable flourophores. We previously developed a simpler method built upon the observation that most photswitchable fluorophores emit an exponentially distributed number of blinks before photobleaching, but its utility was limited by the need to calibrate for the blinking distribution. Here we extend this method by incorporating a machine learning technique known as Expectation-Maximization (EM) and apply it to a statistical mixture model of monomers, dimers and trimers. We show that the protomer fractions and the underlying single-fluorophore blinking distributions can be inferred, simultaneously, from SMLM datasets, obviating the need for an additional calibration and greatly expanding the applicability of this technique. To illustrate the utility of our approach, we benchmark the method on both simulated datasets and experimental datasets assembled from dSTORM images of Alexa-647 labeled DNA nanostructures.
Nest relief in the cryptically-incubating semipalmated sandpiper is quick, but vocal
Authors: Bulla Martin , Muck Christina , Tritscher Daniela , Kempenaers Bart 
Published: August 2021

ABSTRACTBiparental care requires coordination between parents. Such coordination might prove difficult if opportunities to communicate are scarce, which might have led to the evolution of elaborate and noisy nest relief rituals in species facing a low risk of predation. However, whether such conspicuous rituals also evolved in species that avoid predation by relying on crypsis remains unclear. Here, we used a continuous monitoring system to describe nest relief behavior during incubation in an Arctic-breeding shorebird with passive nest defense, the semipalmated sandpiper (Calidris pusilla). We then explored whether nest relief behavior provides information about parental cooperation and predicts incubation effort. We found that incubating parents vocalized twice as much before the arrival of their partner than during other times of incubation. In 75% of nest reliefs, the incubating parent left the nest only after its partner had returned and initiated the nest relief. In these cases, exchanges were quick (25s, median) and shortened over the incubation period by 0.1 – 1.4s per day (95%CI), suggesting that parents became more synchronized. However, nest reliefs were not cryptic. In 90% of exchanges, at least one parent vocalized, and in 20% of nest reliefs the incubating parent left the nest only after its returning partner called instantaneously. In 30% of cases, the returning parent initiated the nest relief with a call; in 39% of these cases, the incubating partner replied. If the partner replied, the next off-nest bout was 1 – 4hr (95%CI) longer than when the partner did not reply, which corresponds to an 8 – 45% increase. Our results indicate that incubating semipalmated sandpipers, which rely on crypsis to avoid nest predation, have quick but acoustically conspicuous nest reliefs. Our results also suggest that vocalizations during nest reliefs may be important for the division of parental duties.LAY SUMMARYBiparental care requires coordination between parents. In species where both parents incubate and nests are visible, parents often perform complex nest relief rituals. Is this also the case in species where nests are cryptic?We video-recorded nest relief behavior at nests of cryptically incubating semipalmated sandpipers.Parents relieved each other quickly, but they vocalized frequently. In 20% of nest reliefs the incubating parent left only after its returning partner called instantaneously. In 30% of cases the returning parent initiated the nest relief with a call. If the partner replied, its next off-nest bout was 1 – 4hr longer than when the partner did not reply, which corresponds to an 8 – 45% increase.Our results suggest that vocalizations during nest relief may be important for the division of parental duties. Further work in sandpipers and other taxa is needed to elucidate the role of parental vocalization in coordinating and synchronizing parental duties.
Chromosome-level Thlaspi arvense genome provides new tools for translational research and for a newly domesticated cash cover crop of the cooler climates
Authors: Nunn Adam , Rodríguez-Arévalo Isaac , Tandukar Zenith , Frels Katherine , Contreras-Garrido Adrián , Carbonell-Bejerano Pablo , Zhang Panpan , Ramos-Cruz Daniela , Jandrasits Katharina , Lanz Christa , Brusa Anthony , Mirouze Marie , Dorn Kevin , Jarvis Brice , Sedbrook John , Wyse Donald L. , Otto Christian , Langenberger David , Stadler Peter F. , Weigel Detlef , Marks M. David , Anderson James A. , Becker Claude , Chopra Ratan 
Published: August 2021

AbstractThlaspi arvense (field pennycress) is being domesticated as a winter annual oilseed crop capable of improving ecosystems and intensifying agricultural productivity without increasing land use. It is a selfing diploid with a short life cycle and is amenable to genetic manipulations, making it an accessible field-based model species for genetics and epigenetics. The availability of a high quality reference genome is vital for understanding pennycress physiology and for clarifying its evolutionary history within the Brassicaceae. Here, we present a chromosome-level genome assembly of var. MN106-Ref with improved gene annotation, and use it to investigate gene structure differences between two accessions (MN108 and Spring32-10) that are highly amenable to genetic transformation. We describe small RNAs, pseudogenes, and transposable elements, and highlight tissue specific expression and methylation patterns. Resequencing of forty wild accessions provides insights into genome-wide genetic variation as well as QTL regions for flowering time and a seedling color phenotype. Altogether, these data will serve as a tool for pennycress improvement in general and for translational research across the Brassicaceae.
A robust method of extraction and GC-MS analysis of Monophenols exhibited UV-B mediated accumulation in Arabidopsis
Authors: Lingwan Maneesh , Masakapalli Shyam Kumar 
Published: August 2021

AbstractStudies on specialised metabolites like phenolics are of immense interest owing to their significance to agriculture, nutrition and health. In plants, phenolics accumulate and exhibits spatial and temporal regulations in response to growth conditions. Robust methodologies aimed at efficient extraction of plant phenolics, their qualitative and quantitative analysis is desired. We optimised the analytical and experimental bottlenecks that captured free, ester, glycoside and wall-bound phenolics after acid or alkali treatments of the tissue extracts and subsequent GC-MS analysis. Higher recovery of phenolics from the methanolic extracts was achieved by through a) Ultrasonication assisted extraction along with Methyl tert-butyl ether (MTBE) enrichment b) nitrogen gas drying and c) their derivatisation using MSTFA for GC-MS analysis. The optimised protocol was tested on Arabidopsis rosette exposed to UV-B radiation (280-315 nm) which triggered enhanced levels of 11 monophenols and might be attributed to photoprotection and other physiological roles. Interestingly, coumaric acid (308 m/z) and caffeic acid (396 m/z) levels were enhanced by 12-14 folds under UV-B. Other phenolics such as cinnamic acid (220 m/z), hydroxybenzoic acid (282 m/z), vanillic acid (312 m/z, gallic acid (458 m/z), ferulic acid (338 m/z), benzoic acid (194 m/z), hydroxycinnamic acid (368 m/z) and protocatechuic acid (370 m/z) also showed elevated levels by about 1 to 4 folds. Notably, vanillin (253 m/z) was detected only in the UV-B exposed tissues. The protocol also comprehensively captured the variations in the levels of ester, glycoside and wall-bounded phenolics with high reproducibility and sensitivity. The robust method of extraction and GC-MS analysis can readily be adopted for studying phenolics in plant systems.
The role of muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury
Authors: Sesillo Francesca Boscolo , Rajesh Varsha , Wong Michelle , Duran Pamela , Baynes Brittni , Laurent Louise C. , Christman Karen L. , Sacco Alessandra , Alperin Marianna 
Published: July 2021

AbstractPelvic floor muscle (PFM) injury during childbirth is a key risk factor for subsequent pelvic floor disorders that affect millions of women worldwide. Muscle stem cells (MuSCs) play a central role in the regeneration of injured skeletal muscles, where they activate, proliferate, and differentiate to assure myogenesis needed for muscle recovery. For robust regenerative function, MuSCs require the support of fibro-adipogenic progenitors (FAPs) and immune cells. To elucidate the role of MuSCs, FAPs, and immune infiltrate in female PFM regeneration, we used radiation to perturb the system and followed PFM recovery in a simulated birth injury (SBI) rat model. Non-irradiated and irradiated rats were euthanized at 3,7, 10, and 28 days after SBI; PFMs were harvested and prepared for immunohistochemistry. Cross sectional area (CSA) of all PFM myofibers 28 days after injury in irradiated animals was significantly lower relative to non-irradiated injured controls, indicating impairment of PFM recovery. Following SBI in non-irradiated animals, the number of MuSCs and FAPs expanded significantly at 7 and 3 days after injury, respectively; this expansion did not occur in irradiated animals at the same time points. CSA of embryonic myosin heavy chain (eMyHC, marker of newly regenerated myofibers) positive fibers was also significantly smaller following SBI in irradiated muscles compared to PFMs from non-irradiated injured controls at 7 days. Our results demonstrate that loss of function and decreased expansion of MuSCs and FAPs associated with irradiation results in impaired PFM recovery, signifying essential roles for MuSCs and FAPs in the regenerative process of female PFMs after birth injury. These findings can inform the identification of novel preventative and therapeutic targets and the development of new treatments for PFM dysfunction and associated pelvic floor disorders.
Plant-associated microbiomes promote nutrient turnover in impoverished substrates of a biodiversity hotspot
Authors: Camargo Antonio P. , Correa de Souza Rafael Soares , Jose Juliana , Gerhardt Isabel R. , Dante Ricardo A. , Mukherjee Supratim , Huntemann Marcel , Kyrpides Nikos C. , Carazzolle Marcelo F. , Arruda Paulo 
Published: August 2021

AbstractThe substrates of the Brazilian campos rupestres have extremely low concentrations of key nutrients, mainly phosphorus, imposing severe restrictions to plant growth. Regardless, this ecosystem harbors enormous biodiversity which raises the question of how nutrients are cycled and acquired by the biosphere. To uncover the nutrient turnover potential of plant-associated microorganisms in the campos rupestres, we investigated the compositions and functions of microbiomes associated with two species of the Velloziaceae family that grow over distinct substrates (soil and rock). Amplicon, metagenomic, and metagenome-assembled genome sequence data showed that the campos rupestres harbor a novel assemblage of plant-associated prokaryotes and fungi. Compositional analysis revealed that the plant-associated soil and rock communities differed in taxonomic structure but shared a core of highly efficient colonizers that were strongly coupled with nutrient mobilization. Investigation of functional and abundance data revealed that the plant hosts actively recruit communities by exuding organic compounds and that the root-associated microbiomes possess a diverse repertoire of phosphorus turnover mechanisms. We also showed that the microbiomes of both plant species encompass novel populations capable of mobilizing nitrogen and that the substrate strongly influences the dynamics of this cycle. Our results show that the interplay between plants and their microbiomes shapes nutrient turnover in the campos rupestres. We highlight that investigation of microbial diversity is fundamental to understand plant fitness in stressful environments.
Social selectivity and social motivation in voles
Authors: Beery Annaliese K. , Lopez Sarah A. , Blandino Katrina L. , Lee Nicole S. , Bourdon Natalie S. , Ahern Todd H. 
Published: July 2021

AbstractSelective relationships are fundamental to humans and many other animals, but relationships between mates, family members, or peers may be mediated differently. We examined connections between social reward and social selectivity, aggression, and oxytocin receptor signaling pathways in rodents that naturally form enduring, selective relationships with mates and peers (prairie voles) or peers (meadow voles). Female prairie and meadow voles worked harder to access familiar vs. unfamiliar individuals, regardless of sex, and huddled extensively with familiar subjects. Male prairie voles also displayed strongly selective huddling preferences for familiar animals, but worked hardest to repeatedly access females vs. males, with no difference in effort by familiarity. This demonstrates a fundamental disconnect between motivation and social selectivity in males, and reveals a striking sex difference in pathways underlying social monogamy. Meadow voles exhibited social preferences but low social motivation, consistent with tolerance rather than reward supporting social groups in this species. Natural variation in oxytocin receptor genotype was associated with oxytocin receptor density, and both genotype and receptor binding predicted individual variation in prosocial and aggressive behaviors. These results provide a basis for understanding species, sex, and individual differences in the mechanisms underlying the role of social reward in social preference.
A Computational Model of the Effect of Short-Term Monocular Deprivation on Binocular Rivalry in the Context of Amblyopia
Authors: Seeliger Norman , Triesch Jochen 
Published: August 2021

AbstractTreatments for amblyopia focus on vision therapy and patching of one eye. Predicting the success of these methods remains difficult, however. Recent research has used binocular rivalry to monitor visual cortical plasticity during occlusion therapy, leading to a successful prediction of the recovery rate of the amblyopic eye. The underlying mechanisms and their relation to neural homeostatic plasticity are not known. Here we propose a spiking neural network to explain the effect of short-term monocular deprivation on binocular rivalry. The model reproduces perceptual switches as observed experimentally. When one eye is occluded, inhibitory plasticity changes the balance between the eyes and leads to longer dominance periods for the eye that has been deprived. The model suggests that homeostatic inhibitory plasticity is a critical component of the observed effects and might play an important role in the recovery from amblyopia.
Degrading intestinal DAF-2 nearly doubles Caenorhabditis elegans lifespan without affecting development or reproduction
Authors: Zhang Yan-Ping , Zhang Wen-Hong , Zhang Pan , Li Qi , Sun Yue , Wang Jia-Wen , Zhang Shao-Bing O. , Cai Tao , Zhan Cheng , Dong Meng-Qiu 
Published: August 2021

SummaryTwenty-eight years following the breakthrough discovery that a single-gene mutation of daf-2 can double the lifespan of Caenorhabditis elegans, it remains unclear where this gene, which encodes an insulin/IGF-1 receptor, is expressed and where it acts to regulate aging. Here, by inserting DNA sequences of fluorescent tags into the genomic locus of daf-2 and that of its downstream transcription factor daf-16, we determined that both genes are expressed in most or all tissues from embryos through adulthood, in line with their diverse functions. Using tissue-specific auxin-induced protein degradation, we determined that both DAF-2 and DAF-16 act in the intestine to regulate organismal aging. Strikingly, loss of DAF-2 in the intestine nearly doubled C. elegans lifespan but did not produce the adverse developmental or reproductive phenotypes associated with genetic daf-2 mutants. These findings unify the mechanism of lifespan regulation by genes and that by dietary restriction, and begin to focus anti-aging research on nutrient supply.Highlightsdaf-2 and daf-16 are expressed in most or all cells of C. elegans using genome editing.DAF-2 and DAF-16 both regulate lifespan from the intestine as determined using auxin-induced protein degradation.Reduced insulin signaling in the intestine nearly doubles C. elegans lifespan without adverse effects on development or reproduction.Lifespan regulation by genes and dietary restriction are unified by intestinal supply of nutrients and metabolism.