bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection
Authors: Goguet Emilie , Olsen Cara H. , Meyer William A. , Ansari Sara , Powers John H. , Conner Tonia L. , Coggins Si’Ana A. , Wang Wei , Wang Richard , Illinik Luca , Edwards Margaret Sanchez , Jackson-Thompson Belinda M. , Hollis-Perry Monique , Wang Gregory , Alcorta Yolanda , Wong Mimi A. , Saunders David , Mohammed Roshila , Balogun Bolatito , Kobi Priscilla , Kosh Lakeesha , Bishop-Lilly Kimberly , Cer Regina Z. , Arnold Catherine E. , Voegtly Logan J. , Fitzpatrick Maren , Luquette Andrea E. , Malagon Francisco , Ortega Orlando , Parmelee Edward , Davies Julian , Lindrose Alyssa R. , Haines-Hull Hannah , Moser Matthew S. , Samuels Emily C. , Tso Marana S. , Graydon Elizabeth K. , Malloy Allison M.W. , Tribble David R. , Burgess Timothy H. , Campbell Wesley , Robinson Sara , Broder Christopher C. , O’Connell Robert J. , Weiss Carol D. , Pollett Simon , Laing Eric D. , Mitre Edward 
Published: August 2023

AbstractWe sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine infections (PVI) acquired during the first Omicron wave in the United States. Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires. Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range. In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.
Stabilization of epithelial β-catenin compromises mammary cell fate acquisition and branching morphogenesis
Authors: Satta Jyoti Prabha , Lan Qiang , Taketo Makoto Mark , Mikkola Marja Liisa 
Published: August 2023

AbstractThe Wnt/β-catenin pathway plays a critical role in cell fate specification, morphogenesis, and stem cell activation across diverse tissues, including the skin. In mammals, the embryonic surface epithelium gives rise to the epidermis, as well as the associated appendages including hair follicles and mammary glands, both of which depend on epithelial Wnt/β-catenin activity for initiation of their development. Later on, Wnts are thought to enhance mammary gland growth and branching while in hair follicles, they are essential for hair shaft formation. Here we report a strong downregulation of epithelial Wnt/β-catenin activity as the mammary bud progresses to branching. We show that forced activation of epithelial β-catenin severely compromises embryonic mammary gland branching. However, the phenotype of conditionalLef1deficient embryos implies that a low level of Wnt/β-catenin activity is necessary for mammary cell survival. Transcriptomic profiling suggests that sustained high β-catenin activity leads to maintenance of mammary bud gene signature at the expense of outgrowth/branching signature. In addition, it leads to upregulation of epidermal differentiation genes. Strikingly, we find a partial switch to hair follicle fate early on upon stabilization of β-catenin suggesting that the level of epithelial Wnt/β-catenin signaling activity may contribute to the choice between skin appendage identities.
Mapping threatened Thai bovids provides opportunities for improved conservation outcomes in Asia
Authors: Horpiencharoen Wantida , Muylaert Renata L. , Marshall Jonathan C. , John Reju Sam , Lynam Antony J. , Riggio Alex , Godfrey Alexander , Ngoprasert Dusit , Gale George A. , Ash Eric , Bisi Francesco , Cremonesi Giacomo , Clements Gopalasamy Reuben , Yindee Marnoch , Shwe Nay Myo , Pin Chanratana , Gray Thomas N. E. , Aung Saw Soe , Nakbun Seree , Manka Stephanie G. , Steinmetz Robert , Phoonjampa Rungnapa , Seuaturien Naret , Phumanee Worrapan , Hayman David T. S. 
Published: August 2023

AbstractWild bovids provide important ecosystem functions throughout their ranges. Five wild bovids remain in Thailand: gaur (Bos gaurus), banteng (Bos javanicus), wild water buffalo (Bubalus arnee), mainland serow (Capricornis sumatraensis) and Chinese goral (Naemorhedus griseus). However, their populations and habitats have declined substantially and become fragmented. Here, we identify potentially suitable habitat for these threatened bovids using ecological niche models and quantify how much suitable area remains within protected areas. We combined species occurrence data with environmental variables and used spatially-restricted Biotic-Abiotic-Mobility frameworks with species-specific and single large accessible areas. We used ensembles from eight algorithms for generating maps and out-of-sample predictions to validate model performance against new data. Gaur, banteng, and buffalo models performed well throughout the entire distribution (≥62%) and in Thailand (≥80%). Mainland serow and Chinese goral performed poorly for the entire distribution and in Thailand, though a 5 km movement buffer markedly improved model performance for serow. Particularly large suitable areas were in Thailand and India for gaur, Cambodia and Thailand for banteng, and India for buffalo. Over 50% of overall suitable habitat is located outside protected areas, with just 9% for buffalo in Thai protected areas, highlighting area for potential habitat management and conflict mitigation.
AlphaFold2 predicts interactions amidst confounding structural compatibility
Authors: Martin Juliette 
Published: August 2023

AbstractPredicting physical interactions is one of the holy grails of computational biology, galvanized by rapid advancements in deep learning. AlphaFold2, although not developed with this goal, seems promising in this respect. Here, I test the prediction capability of AlphaFold2 on a very challenging data set, where proteins are structurally compatible, even when they do not interact. AlphaFold2 achieves high discrimination between interacting and non-interacting proteins, and the cases of misclassifications can either be rescued by revisiting the input sequences or can suggest false positives and negatives in the data set. Alphafold2 is thus not impaired by the compatibility between protein structures and has the potential to be applied at large scale.
Systematic creation and phenotyping of Mendelian disease models inC. elegans: towards large-scale drug repurposing
Authors: O’Brien Thomas J. , Barlow Ida L. , Feriani Luigi , Brown André E.X. 
Published: August 2023

AbstractThere are thousands of Mendelian diseases with more being discovered weekly and the majority have no approved treatments. To address this need, we require scalable approaches that are relatively inexpensive compared to traditional drug development. In the absence of a validated drug target, phenotypic screening in model organisms provides a route for identifying candidate treatments. Success requires a screenable phenotype, however the right phenotype and assay may not be obvious for pleiotropic neuromuscular disorders. Here we show that high-throughput imaging and quantitative phenotyping can be conducted systematically on a panel ofC. elegansdisease model strains. We used CRISPR genome-editing to create 25 worm models of human Mendelian diseases and phenotyped them using a single standardised assay. All but two strains were significantly different from wild-type controls in at least one feature. The observed phenotypes were diverse, but mutations of genes predicted to have related functions in their human orthologs led to similar behavioural differences in worms. As a proof-of-concept, we performed a drug repurposing screen of an FDA approved compound library, and identified two compounds that rescued the behavioural phenotype of a model of UNC80 deficiency. Our results show that a single assay to measure multiple phenotypes can be applied systematically to diverse Mendelian disease models. The relatively short time and low cost associated with creating and phenotyping multiple strains suggests that high-throughput worm tracking could provide a scalable approach to drug repurposing commensurate with the number of Mendelian diseases.
Sandy: A user-friendly and versatile NGS simulator to facilitate sequencing assay design and optimization
Authors: Miller Thiago L. A. , Conceição Helena B. , Mercuri Rafael L. , Santos Felipe R. C. , Barreiro Rodrigo , Buzzo José Leonel , Rego Fernanda O. , Guardia Gabriela , Galante Pedro A. F. 
Published: August 2023

ABSTRACTNext-generation sequencing (NGS) is currently the gold standard technique for large-scale genome and transcriptome studies. However, the downstream processing of NGS data is a critical bottleneck that requires difficult decisions regarding data analysis methods and parameters. Simulated or synthetic NGS datasets are practical and cost-effective alternatives for overcoming these difficulties. Simulated NGS datasets have known true values and provide a standardized scenario for driving the development of data analysis methodologies and tuning cut-off values. Although tools for simulating NGS data are available, they have limitations in terms of their overall usability and documentation. Here, we present Sandy, an open-source simulator that generates synthetic reads that mimic DNA or RNA next-generation sequencing on the Illumina, Oxford Nanopore, and Pacific Bioscience platforms. Sandy is designed to be user-friendly, computationally efficient, and capable of simulating data resembling a wide range of features of real NGS assays, including sequencing quality, genomic variations, and gene expression profiles per tissue. To demonstrate Sandy’s versatility, we used it to address two critical questions in designing an NGS assay: (i) How many reads should be sequenced to ensure unbiased analysis of gene expression in an RNA sequencing run? (ii) What is the lowest genome coverage required to identify most (90%) of the single nucleotide variants and structural variations in whole-genome sequencing? In summary, Sandy is an ideal tool for assessing and validating pipelines for processing, optimizing results, and defining the costs of NGS assays. Sandy runs on Linux, MacOS, and Microsoft Windows and can provide feasible results, even on personal computers. Availability: Sandy is freely available athttps://galantelab.github.io/sandy.
Modulation of cannabinoid receptor 2 alters neuroinflammation and reduces formation of alpha-synuclein aggregates in a rat model of nigral synucleinopathy
Authors: Joers Valerie , Murray Benjamin C , McLaughlin Caroline , Oliver Danielle , Staley Hannah , Coronado Jazmyn , Achat-Mendes Cindy , Golshani Sanam , Kelly Sean D. , Goodson Matthew , Lee Danica , Manfredsson Fredric P. , Moore Bob M. , Tansey Malú Gámez 
Published: August 2023

ABSTRACTResearch into the disequilibrium of microglial phenotypes has become an area of intense focus in neurodegenerative disease as a potential mechanism that contributes to chronic neuroinflammation and neuronal loss in Parkinson’s disease (PD). There is growing evidence that neuroinflammation accompanies and may promote progression of alpha-synuclein (Asyn)-induced nigral dopaminergic (DA) degeneration. From a therapeutic perspective, development of immunomodulatory strategies that dampen overproduction of pro-inflammatory cytokines from chronically activated immune cells and induce a pro-phagocytic phenotype is expected to promote Asyn removal and protect vulnerable neurons. Cannabinoid receptor-2 (CB2) is highly expressed on activated microglia and peripheral immune cells, is upregulated in the substantia nigra of individuals with PD and in mouse models of nigral degeneration. Furthermore, modulation of CB2 protects against rotenone-induced nigral degeneration; however, CB2 has not been pharmacologically and selectively targeted in an Asyn model of PD. Here, we report that 7 weeks of peripheral administration of CB2 inverse agonist SMM-189 reduced phosphorylated (pSer129) alpha-synuclein in the substantia nigra compared to vehicle treatment. Additionally, SMM-189 delayed Asyn-induced immune cell infiltration into the brain as determined by flow cytometry, increased CD68 protein expression, and elevated wound-healing-immune-mediator gene expression. Additionally, peripheral immune cells increased wound-healing non-classical monocytes and decreased pro-inflammatory classical monocytes.In vitroanalysis of RAW264.7 macrophages treated with lipopolysaccharide (LPS) and SMM-189 revealed increased phagocytosis as measured by the uptake of fluorescence of pHrodoE. colibioparticles. Together, results suggest that targeting CB2 with SMM-189 skews immune cell function toward a phagocytic phenotype and reduces toxic aggregated species of Asyn. Our novel findings demonstrate that CB2 may be a target to modulate inflammatory and immune responses in proteinopathies.
The genome of the colonial hydroidHydractiniareveals their stem cells utilize a toolkit of evolutionarily shared genes with all animals
Authors: Schnitzler Christine E. , Chang E. Sally , Waletich Justin , Quiroga-Artigas Gonzalo , Wong Wai Yee , Nguyen Anh-Dao , Barreira Sofia N. , Doonan Liam , Gonzalez Paul , Koren Sergey , Gahan James M. , Sanders Steven M. , Bradshaw Brian , DuBuc Timothy Q. , Febrimarsa  , Jong Danielle de , Nawrocki Eric P. , Larson Alexandra , Klasfeld Samantha , Gornik Sebastian G. , Moreland R. Travis , Wolfsberg Tyra G. , Phillippy Adam M. , Mullikin James C. , Simakov Oleg , Cartwright Paulyn , Nicotra Matthew , Frank Uri , Baxevanis Andreas D. 
Published: August 2023

ABSTRACTHydractiniais a colonial marine hydroid that exhibits remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of twoHydractiniaspecies,H. symbiolongicarpusandH. echinata, placing them in a comparative evolutionary framework with other cnidarian genomes. We also generated and annotated a single-cell transcriptomic atlas for adult maleH. symbiolongicarpusand identified cell type markers for all major cell types, including key i-cell markers. Orthology analyses based on the markers revealed thatHydractinia’s i-cells are highly enriched in genes that are widely shared amongst animals, a striking finding given thatHydractiniahas a higher proportion of phylum-specific genes than any of the other 41 animals in our orthology analysis. These results indicate thatHydractinia’s stem cells and early progenitor cells may use a toolkit shared with all animals, making it a promising model organism for future exploration of stem cell biology and regenerative medicine. The genomic and transcriptomic resources forHydractiniapresented here will enable further studies of their regenerative capacity, colonial morphology, and ability to distinguish self from non-self.
Long-term impacts on estuarine benthic assemblages 4.2 years after a mine tailing spill in SE Brazil
Authors: Coppo Gabriel C. , Gabriel Fabrício A. , Mazzuco Ana Carolina A. , Queiroz Hermano M. , Barcellos Diego , Ferreira Tiago O. , Bernardino Angelo F. 
Published: August 2023

AbstractThe Rio Doce estuary was critically impacted in 2015 by the world’s largest mining tailing spill, with still unclear long-term effects. Here we present a long-term (2015 to 2020) assessment of estuarine benthic assemblages, where Annelida and Mollusca were dominant (52.6% and 26.3%, respectively). Our results demonstrated that the density and richness of benthic taxa decreased in response to an increase in potentially toxic elements concentrations, suggesting a chronic pollution effect that lasted for at least 4.2 years in the estuary. Our data demonstrated that despite the decline in sediment potentially toxic elements concentration over time, there was a continued low habitat quality for the benthic fauna characterized by a reduction of 96% on macroinvertebrate density and 48% on species richness. The long-term impacts on benthic macrofauna highlight that water quality levels can misguide impact assessment programs, and reveal that mine tailings impacts persist for many years in estuarine ecosystems.
Synchronicity in zebrafish locomotive circuit development mediated by electrical pacemaker interneurons
Authors: Miles Kaleb D. , Barker Chase M. , Appel Bruce H. , Doll Caleb A. 
Published: August 2023

AbstractThe earliest motor output in vertebrate animals is generated by clusters of early-born motor neurons that occupy distinct regions of the spinal cord, innervating stereotyped muscle groups. Even the simplest movements require coordinated activity across these motor pools, yet motor neurons are not directly interconnected and instead project to the periphery. Instead, emerging motor circuits might be synchronized by pacemaker interneurons. We hypothesize that pacemaker interneurons are required for synchronization of motor neuron activity throughout the spinal cord, coupling motor pools through electrical gap junctions to ultimately drive coordinated motor behavior. With functional imaging in the embryonic zebrafish spinal cord, we show that ipsilateral caudal interneurons possess periodic activity profiles prior to widespread motor circuit activity that transition to synchronized Ca2+events in motor neurons throughout the spinal cord. Importantly, we also show that blockade of electrical gap junctions and ablation of pioneer pacemakers leads to desynchronization in developing motor circuits. Further, we use a genetic model of hyperactivity to gain critical insight into the consequences of errors in motor circuit formation and function, finding that Fragile X syndrome (FXS) model mutant zebrafish are hyperexcitable from the earliest phases of spontaneous behavior, show reduced sensitivity to blockade of electrical gap junctions, and have increased expression of the gap junction protein Connexin 36. Taken together, our work highlights the importance of pacemakers in the development of motor circuits and suggests that the origins of hyperactivity in neurodevelopmental disorders may be established during the initiation of motor circuit formation.
CNTN4 modulates neural elongation through interplay with APP
Authors: Bamford Rosemary A. , Zuko Amila , Sprengers Jan J. , Post Harm , Taggenbrock Renske L. R. E. , Mehr Annika , Jones Owen J. R. , Kudzinskas Aurimas , Gandawijaya Josan , Eve Madeline , Müller Ulrike C. , Kas Martien J. , Burbach J. Peter H. , Oguro-Ando Asami 
Published: August 2023

AbstractThe neuronal cell adhesion molecule contactin-4 (CNTN4) has been genetically linked to autism spectrum disorders (ASD) and other psychiatric disorders. TheCntn4-deficient mouse model has previously shown that CNTN4 has important roles in axon guidance and synaptic plasticity in the hippocampus. However, the pathogenesis and functional role of CNTN4 in the cortex have not yet been investigated.Using Nissl staining, immunohistochemistry and Golgi staining the motor cortex ofCntn4-/-mice was analysed for abnormalities. Interacting partners of CNTN4 were identified by immunoprecipitation and mass spectrometry. Further analysis of the interaction between CNTN4 and APP utilised knockout human cells generated via CRISPR-Cas9 gene editing.Our study newly identified reduced cortical thickness in the motor cortex ofCntn4-/-mice, but cortical cell migration and differentiation were unaffected. Significant morphological changes were observed in neurons in the M1 region of the motor cortex, indicating that CNTN4 is also involved in the morphology and spine density of neurons in the motor cortex. Furthermore, mass spectrometry analysis identified an interaction partner for CNTN4, and we confirmed an interaction between CNTN4 and APP. Knockout human cells of CNTN4 and/or APP revealed a relationship between CNTN4 and APP.This study demonstrates that CNTN4 contributes to cortical development, and that its binding and interplay with APP controls neural elongation. This is an important finding for understanding the function of APP, a target protein for Alzheimer’s disease. The binding between Cntn4 and APP, which is involved in neurodevelopment, is essential for healthy nerve outgrowth.
Theoretical minimum uncertainty of modulation enhanced spinning disk confocal microscopy
Authors: Kalisvaart Dylan , Hung Shih-Te , Smith Carlas S. 
Published: August 2023

Modulation enhanced single-molecule localization microscopy (meSMLM), where emitters are sparsely activated with patterned illumination, increases the localization precision over SMLM. Furthermore, meSMLM improves the resolution over structured illumination microscopy while reducing the required amount of illumination patterns. These factors motivate enabling meSMLM in existing systems which employ patterned illumination intensity. Here, we introduce SpinFlux: modulation enhanced localization for spinning disk confocal microscopy. SpinFlux uses a spinning disk with pinholes in its illumination and emission paths, to illuminate select regions in the sample during each measurement. The resulting intensity-modulated emission signal is analyzed to localize emitters with improved precision. We derive a statistical image formation model for SpinFlux and we quantify the theoretical minimum uncertainty, in terms of the Cramér-Rao lower bound, for various illumination pattern configurations. We find that SpinFlux requires multiple patterns to improve the localization precision over SMLM, with the maximum improvement being 1.17 when using a single pattern. When using two pinholes on opposing sides of the emitter position, thex-localization precision can locally be improved 2.62-fold over SMLM, whereas they-precision is improved by maximally a factor 1.12. When using pinholes in a triangular configuration around the emitter position, the localization precision is balanced over thexandy-directions at approximately a twofold local improvement over SMLM, at the cost of suboptimal precision in each individual direction. When doughnut-shaped illumination patterns, created with a phase mask in the illumination and emission paths, are used for SpinFlux, the local precision improvement over SMLM is increased 3.5-fold in thex- andy-directions. While localization on ISM data ideally results in an average global improvement of 1.48 over SMLM, or 2.10 with Fourier reweighting, SpinFlux is the method of choice for local refinements of the localization precision.Why it matters: One of the main objectives of singlemolecule localization microscopy (SMLM) is to improve the precision with which single molecules can be localized. This has been successfully achieved through modulation enhanced SMLM, which uses patterned illumination to increase the information content of signal photons. However, this technique relies on setups with increased technical complexity over SMLM. With SpinFlux, we locally enable a twoto 3.5-fold precision improvement over singlemolecule localization microscopy, which can be achieved with only minor modifications to existing spinning disk confocal microscopy setups (e.g. a phase mask in the illumination and emission paths). In addition, our modeling framework enables evaluation of a wide variety of spinning disk setups and therefore paves the way for optimal spinning disk design.