bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of a multi-target TaqMan qPCR method for detection ofBorrelia burgdorferisensu lato
Authors: Masséglia Sébastien , René-Martellet Magalie , Rates Maxime , Hizo-Teufel Cecilia , Fingerle Volker , Margos Gabriele , Bailly Xavier 
Published: July 2023

AbstractReliable detection of bacteria belonging to theBorrelia burgdorferisensu lato species complex in vertebrate reservoirs, tick vectors, and patients is key to answer questions regarding Lyme borreliosis epidemiology. Nevertheless, the description of characteristics of qPCRs for the detection ofB. burgdorferis. l. are often limited. This study covers the development and validation of two duplex taqman qPCR assays used to target four markers on the chromosome of genospecies ofB. burgdorferis. l..Analytical specificity was determined with a panel of spirochete strains. qPCR characteristics were specified using water or tick DNA spiked with controlled quantities of the targeted DNA sequences ofB. afzelii,B. burgdorferisensu stricto orB. bavariensis. The effectiveness of detection results was finally evaluated using DNA extracted from ticks and biopsies from mammals whose infectious status had been determined by other detection assays.The developed qPCR assays allow exclusive detection ofB. burgdorferis. l. with the exception of the M16 marker which also detect relapsing feverBorreliaspecies. The limit of detection is between 10 and 40 copies per qPCR reaction depending on the sample type, theB. burgdorferigenospecies and the targeted marker. Detection tests performed on various kind of samples illustrated the accuracy and robustness of our qPCR assays.Within the defined limits, this multi-target qPCR method allows a versatile detection ofB. burgdorferis. l., regardless of the genospecies and the sample material analyzed, with a sensitivity that would be compatible with most applications and a reproducibility of 100% under measurement conditions and limits of detection, thereby limiting result ambiguities.HighlightsFour qPCR assays used in duplex were developed to detectBorrelia burgdorferisensu lato. The limits of detection and quantification were defined according to state of the art standards. The specifications allow to detectB. burgdorferisensu lato from different sampling sources.
Molecular Surface Descriptors to Predict Antibody Developability
Authors: Park Eliott , Izadi Saeed 
Published: July 2023

AbstractUnderstanding the molecular surface properties of monoclonal antibodies (mAbs) is crucial for determining their function, affinity, and developability. Yet, robust methods to accurately represent the key structural and biophysical features of mAbs on their molecular surface are still limited. Here, we introduce MolDesk, a set of molecular surface descriptors specifically designed for predicting antibody developability characteristics. We assess the performance of these descriptors by directly benchmarking their correlations with an extensive array ofin vitroandin vivodata, including viscosity at high concentration, aggregation, hydrophobic interaction chromatography (HIC), human pharmacokinetic (PK) clearance, Heparin retention time, and polyspecificity. Additionally, we investigate the sensitivity of these surface descriptors to methodological nuances, such as the choice of interior dielectric constant for electrostatic potential calculations, residue-level hydrophobicity scales, initial antibody structure models, and the impact of conformational sampling. Based on our benchmarking analysis, we propose sixin silicodevelopability rules that leverage these molecular surface descriptors and demonstrate their superior ability to predict the clinical progression of therapeutic antibodies compared to established models like TAP.1
Taste shaped the use of botanical drugs
Authors: Leonti Marco , Baker Joanna , Staub Peter , Casu Laura , Hawkins Julie 
Published: July 2023

AbstractThe perception of taste and flavour (a combination of taste, smell and chemesthesis) here also referred to as chemosensation, enables animals to find high-value foods and avoid toxins. Humans have learned to use unpalatable and toxic substances as medicines, yet the importance of chemosensation in this process is poorly understood. Here we generate tasting-panel data for botanical drugs and apply phylogenetic generalised linear mixed models to test whether intensity and complexity of chemosensory qualities as well as particular tastes and flavours can predict ancient Graeco-Roman drug use. We found chemosensation to be strongly predictive of therapeutic use: botanical drugs with high therapeutic versatility have simple yet intense tastes and flavours, and 21 of 22 chemosensory qualities predicted at least one therapeutic use. In addition to the common notion of bitter tasting medicines, we also found starchy, musky, sweet, cooling, and soapy drugs associated with versatility. In ancient Greece and Rome, illness was thought to arise from imbalance in bodily fluids or humours, yet our study suggests that uses of drugs were based on observed physiological effects that are often consistent with modern understanding of chemesthesis and taste receptor pharmacology.
Dynamic corticothalamic modulation of the somatosensory thalamocortical circuit during wakefulness
Authors: Dimwamwa Elaida D. , Pala Aurélie , Chundru Vivek , Wright Nathaniel C. , Stanley Garrett B. 
Published: July 2023

AbstractThe feedback projections from cortical layer 6 (L6CT) to sensory thalamus have long been implicated in playing a primary role in gating sensory signaling but remain poorly understood. To causally elucidate the full range of effects of these projections, we targeted silicon probe recordings to the whisker thalamocortical circuit of awake mice selectively expressing Channelrhodopsin-2 in L6CT neurons. Through optogenetic manipulation of L6CT neurons, multi-site electrophysiological recordings, and modeling of L6CT circuitry, we establish L6CT neurons as dynamic modulators of ongoing spiking in the ventro-posterior-medial nucleus of thalamus (VPm), either suppressing or enhancing VPm spiking depending on L6CT neurons’ firing rate and synchrony. Differential effects across the cortical excitatory and inhibitory sub-populations point to an overall influence of L6CT feedback on cortical excitability that could have profound implications for regulating sensory signaling across a range of ethologically relevant conditions.
mEthAE: an Explainable AutoEncoder for methylation data
Authors: Katz Sonja , Martins dos Santos Vitor A.P. , Saccenti Edoardo , Roshchupkin Gennady V. 
Published: July 2023

1AbstractIn the quest to unravel the mysteries of our epigenetic landscape, researchers are continually challenged by the relationships among CpG sites. Traditional approaches are often limited by the immense complexity and high dimensionality of DNA methylation data. To address this problem, deep learning algorithms, such as autoencoders, are increasingly applied to capture the complex patterns and reduce dimensionality into latent space. In this pioneering study, we introduce an innovative chromosome-wise autoencoder, termed mEthAE, specifically designed for the interpretive reduction of methylation data. mEthAE achieves an impressive 400-fold reduction in data dimensions without compromising on reconstruction accuracy or predictive power in the latent space. In attempt to go beyond mere data compression, we developed a perturbation-based method for interpretation of latent dimensions. Through our approach we identified clusters of CpG sites that exhibit strong connections across all latent dimensions, which we refer to as ‘global CpGs’. Remarkably, these global CpGs are more frequently highlighted in epigenome-wide association studies (EWAS), suggesting our method’s ability to pinpoint biologically significant CpG sites. Our findings reveal a surprising lack of correlation patterns, or even physical proximity on the chromosome among these connected CpGs. This leads us to propose an intriguing hypothesis: our autoencoder may be detecting complex, long-range, non-linear interaction patterns among CpGs. These patterns, largely uncharacterised in current epigenetic research, hold the potential to shed new light on our understanding of epigenetics. In conclusion, this study not only showcases the power of autoencoders in untangling the complexities of epigenetic data but also opens up new avenues for understanding the hidden connections within CpGs.
Network and structural analysis of quail mucins with expression pattern of MUC1 and MUC4 in the intestines of the Iraqi Common Quail (Coturnix Coturnix)
Authors: Almhanna Hazem , Mahdi AL-Mahmodi Aqeel Mohsin , Kadhim Abdulrazzaq B , Kumar Arun HS 
Published: July 2023

AbstractBackgroundMucins have vital pathophysiological role in gastrointestinal tract (GIT) of avian and other species. However, despite this very little is known about the types of mucins expressed in quail GIT. Hence in this study we examined the expression pattern of mucins (MUC1, and MUC4) in the GIT of the Iraqi Common Quail (Coturnix Coturnix) and performed the network and structural analysis of all reported types of mucins in various breeds of quails.Materials and methodsThis study protocol was approved by the animal ethics research committee of the College of Veterinary Medicine, University of Al-Qadisiyah, Iraq. Fresh samples of small and large intestines were used for histological and gene expression analysis of MUC1, and MUC4. Network and structural analysis of all reported types of mucins in quails was performed using the STRING Database, Chimera software and PrankWeb-Ligand Binding Site Prediction tool.ResultsThe histological analysis using Alcian blue and PAS stains indicated that most mucins in the intestines of quails were of the acidic mucin type, with minimal prevalence of neutral mucins. The expression of acidic mucins was relatively higher in the duodenum, ileum, caecum, and colon, while the jejunum showed a relatively higher expression of neutral mucins. Gene expression analysis revealed higher expression levels of MUC1 and MUC4 mRNA in the jejunum and colon, with its least expression in the duodenum and ilium. Network analysis indicated predominantly mucin-mucin interactions, with MUC 1, 15, 16 and 24 showing preferential homologous networks while the MUC 2, 4, 5 and 6 showed heterologous networks. Detailed evaluation of intermolecular hydrogen bond formation highlighted the interactions between specific mucin combinations, with certain combinations showing higher affinity, such as MUC5A-MUC6, MUC5A-MUC5B, and MUC5B-MUC6. In contrast, MUC15, MUC16, and MUC24 exhibited limited interactions with other mucin types. Binding site analysis indicated that MUC5B and MUC6 had the most number of binding sites with high probability scores, while MUC2, MUC4, and MUC5A showed lower probability scores despite having more binding sites. In contrast MUC 1, 15, and 16 had very few binding sites (<3 binding sites) all with very low probability scores.ConclusionThe findings of this study provide valuable insights into the composition, expression, network interactions, and binding sites of mucins in the quails, contributing to the understanding of mucin-related processes in gastrointestinal physiology and potential implications for gastrointestinal diseases.
Measuring RBC deformability and its heterogeneity using a fast microfluidic device
Authors: Kumari Savita , Mehendale Ninad , Roy Tanusri , Sen Shamik , Mitra Dhrubaditya , Paul Debjani 
Published: July 2023

SUMMARYWe report a high-throughput microfluidic device to determine the Young’s modulus of single red blood cells (RBCs). Our device consists of a single channel opening into a funnel, with a semi-circular obstacle placed at the mouth of the funnel. As a RBC passes the obstacle, it deflects from its original path. Using populations of artificially-stiffened RBCs, we show that the stiffer RBCs deflect more compared to the healthy RBCs. We then generate a calibration curve that maps each RBC trajectory to its Young’s modulus obtained using an atomic force microscope. Finally, we sort a mixed population of RBCs based on their deformability alone. Our device could potentially be further miniaturized to sort and obtain the elastic constants of nanoscale objects, such exosomes, whose shape change is difficult to monitor by optical microscopy.
Trophic diversity and evolution in Enantiornithes: a synthesis including new insights from Bohaiornithidae
Authors: Miller Case Vincent , Bright Jen A. , Wang Xiaoli , Zheng Xiaoting , Pittman Michael 
Published: July 2023

AbstractThe “opposite birds” Enantiornithines were the dominant birds of the Mesozoic, but our understanding of their ecology is still tenuous. In particular, diets of enantiornithine species have remained speculative until recently. While this new work has been effective at determining diet within groups of enantiornithines, diet data thus far has been too sparse to comment on larger trends in the diversity and evolution of enantiornithine ecology. We introduce new data on the enantiornithine family Bohaiornithidae, famous for their large size and strong teeth and claws. In tandem with previously-published data on the earlier-diverging pengornithids and later-diverging longipterygids, we comment on the breadth of enantiornithine ecology and potential patterns in which it evolved. Body mass, jaw mechanical advantage, finite element analysis of the jaw, and traditional morphometrics of the claws and skull are compared between bohaiornithids and living birds. The sample size for living bird body mass is over ten times larger than previous studies on longipterygid and pengornithid diet, with implications in interpreting their results. We find bohaiornithids to be ecologically diverse:BohaiornisandParabohaiornisare similar to living plant-eating birds;Longusunguisresembles raptorial carnivores;Zhouornisis similar to both fruit-eating birds and generalist feeders; andShenqiornisandSulcavisplausibly ate fish, plants, or a mix of both. This ecological diversity is wider than any other enantiornithine family studied previously, which may be driven by strengthening of the jaw relative to other early birds. This strong jaw would allow bohaiornithids to eat harder foods than other birds at the time, but their jaws were weaker than most “strong-jawed” living birds. With these reconstructions of diet in Bohaiornithidae, there is quantitative support for enantiornithines inhabiting nearly every trophic level. By combining these reconstructions with past dietary predictions for Longipterygidae and Pengornithidae, we predict the ancestral enantiornithine bird to have been a generalist which ate a wide variety of foods. This would suggest that the ecological diversity of enantiornithine birds represents specialisation in taking foods their ancestors were already eating, rather than many dramatic changes in diet. However, more quantitative data from across the enantiornithine tree is needed to refine this prediction. By the Early Cretaceous, enantiornithine birds had diversified into a variety of ecological niches in a similar way to crown birds after the K-Pg extinction, adding to the body of evidence that traits unique to crown birds (e.g. a toothless beak or cranial kinesis) cannot completely explain their ecological success.
Phage inducible chromosomal minimalist island (PICMI), a family of satellites of marine virulent phages
Authors: Barcia-Cruz Rubén , Goudenège David , Moura de Sousa Jorge A. , Piel Damien , Marbouty Martial , Rocha Eduardo P.C. , Roux Frédérique Le 
Published: July 2023

SUMMARYPhage satellites are genetic elements that hijack the phage machinery for their own dissemination. However, only few phage satellites have been characterized, and mechanisms by which they influence microbial evolution in nature are unclear. Here we identify a new family of satellites, the Phage Inducible Chromosomal Minimalist Island (PICMI), which is broadly distributed in the marine bacteriaVibrionaceae. PICMI is characterized by reduced gene content, does not encode genes for capsid remodeling and packages its DNA as a concatemer. PICMI is integrated in the bacterial host genome at the end of thefisregulator and encodes three core proteins necessary for excision and replication. PICMI is dependent on virulent phage particles to spread to other bacteria and confers host protection from other competitive phages, without interfering with its helper phage. The discovery of PICMI strongly suggests that phages, including virulent ones, play important roles for mobility of phage defense elements.
C2C12 muscle myotubes, but not kidney proximal tubule HK-2 cells, elevate erythritol synthesis in response to oxidative stress
Authors: Ortiz Semira R. , Field Martha S. 
Published: July 2023

AbstractBackgroundAs a biomarker, elevated serum erythritol predicts type 2 diabetes and cardiovascular disease onset. Erythritol was recently shown to be a product of human glucose metabolism through the pentose phosphate pathway. The regulation of erythritol synthesis from glucose has been explored in cancer cells, but not in non-transformed cells.ObjectiveThe kidneys and skeletal muscle have increased erythritol content in response to dietary sucrose, which suggests that they may significantly contribute to circulating erythritol levels. In the present study, we evaluated if conditions that promote erythritol synthesis in cancer cells are consistent in skeletal muscle and kidney cells.MethodsC2C12 myotubules were used as a model for skeletal muscle and HK-2 human proximal tubule cells were used to model kidney. C2C12 cells were exposed to high-or low-glucose conditions. Both C2C12 and HK-2 cells were exposed to the free radical generator menadione, then intracellular reactive oxygen species (ROS) and erythritol were measured. Intracellular sorbitol levels were also measured because increased polyol flux is also observed after exposure to excess glucose and oxidative stress.ResultsIntracellular erythritol was significantly elevated in C2C12 cells following both high glucose and menadione treatment. In contrast, HK-2 cells did not increase erythritol synthesis in response to oxidative stress. Generation of ROS through hydrogen peroxide (H2O2) exposure elevated sorbitol levels in both C2C12 and HK-2 cells, whereas generation of radicals with menadione treatment did not affect sorbitol production in either cell type.ConclusionsThese findings highlight that the factors contributing to elevated erythritol synthesis vary between cell types. More specifically, these studies demonstrate that muscle cells increase erythritol synthesis in response to both high glucose in culture medium and oxidative stress, whereas kidney cells increase erythritol synthesis only in response to high glucose.
A modular chemigenetic calcium indicator enables in vivo functional imaging with near-infrared light
Authors: Farrants Helen , Shuai Yichun , Lemon William C. , Hernandez Christian Monroy , Yang Shang , Patel Ronak , Qiao Guanda , Frei Michelle S. , Grimm Jonathan B. , Hanson Timothy L. , Tomaska Filip , Turner Glenn C. , Stringer Carsen , Keller Philipp J. , Beyene Abraham G. , Chen Yao , Liang Yajie , Lavis Luke D. , Schreiter Eric R. 
Published: July 2023

AbstractGenetically encoded fluorescent calcium indicators have revolutionized neuroscience and other biological fields by allowing cellular-resolution recording of physiology during behavior. However, we currently lack bright, genetically targetable indicators in the near infrared that can be used in animals. Here, we describe WHaloCaMP, a modular chemigenetic calcium indicator built from bright dye-ligands and protein sensor domains that can be genetically targeted to specific cell populations. Fluorescence change in WHaloCaMP results from reversible quenching of the bound dye via a strategically placed tryptophan. WHaloCaMP is compatible with rhodamine dye-ligands that fluoresce from green to near-infrared, including several dye-ligands that efficiently label the central nervous system in animals. When bound to a near-infrared dye-ligand, WHaloCaMP1a is more than twice as bright as jGCaMP8s, and shows a 7× increase in fluorescence intensity and a 2.1 ns increase in fluorescence lifetime upon calcium binding. We use WHaloCaMP1a with near-infrared fluorescence emission to image Ca2+responses in flies and mice, to perform three-color multiplexed functional imaging of hundreds of neurons and astrocytes in zebrafish larvae, and to quantitate calcium concentration using fluorescence lifetime imaging microscopy (FLIM).
Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats
Authors: Leaker Ben D. , Wang Yongtao , Tam Joshua , Anderson R. Rox 
Published: July 2023

AbstractPrecision-cut liver slices (PCLS) are increasingly used as a model to investigate anti-fibrotic therapies. However, many studies use PCLS from healthy animals treated with pro-fibrotic stimuli in culture, which reflects only the early stages of fibrosis. The performance of PCLS from cirrhotic animals has not been well characterized and there is no consensus on optimal culture conditions. In this study, we report a method for the collection and culture of cirrhotic PCLS and compare the effect of common culture conditions on viability, function, and gene expression. Additionally, we compared three methods of RNA isolation and identified a protocol with high yield and purity. We observed significantly increased albumin production when cultured with insulin and dexamethasone, and when incubated on a rocking platform. Culturing with insulin and dexamethasone maintained gene expression closer to the levels in fresh slices. However, despite stable viability and function up to 4 days, we found significant changes in expression by day 2. Due to the influence of matrix stiffness on fibrosis and hepatocellular function, it is important to evaluate prospective anti-fibrotic therapies in a platform that preserves tissue biomechanics. PCLS from cirrhotic animals represent a promising tool for the development of treatments for chronic liver disease.
Scalable querying of human cell atlases via a foundational model reveals commonalities across fibrosis-associated macrophages
Authors: Heimberg Graham , Kuo Tony , DePianto Daryle , Heigl Tobias , Diamant Nathaniel , Salem Omar , Scalia Gabriele , Biancalani Tommaso , Turley Shannon , Rock Jason , Bravo Héctor Corrada , Kaminker Josh , Heiden Jason A. Vander , Regev Aviv 
Published: July 2023

AbstractSingle-cell RNA-seq (scRNA-seq) studies have profiled over 100 million human cells across diseases, developmental stages, and perturbations to date. A singular view of this vast and growing expression landscape could help reveal novel associations between cell states and diseases, discover cell states in unexpected tissue contexts, and relatein vivocells toin vitromodels. However, these require a common, scalable representation of cell profiles from across the body, a general measure of their similarity, and an efficient way to query these data. Here, we present SCimilarity, a metric learning framework to learn and search a unified and interpretable representation that annotates cell types and instantaneously queries for a cell state across tens of millions of profiles. We demonstrate SCimilarity on a 22.7 million cell corpus assembled across 399 published scRNA-seq studies, showing accurate integration, annotation and querying. We experimentally validated SCimilarity by querying across tissues for a macrophage subset originally identified in interstitial lung disease, and showing that cells with similar profiles are found in other fibrotic diseases, tissues, and a 3D hydrogel system, which we then repurposed to yield this cell statein vitro. SCimilarity serves as a foundational model for single cell gene expression data and enables researchers to query for similar cellular states across the entire human body, providing a powerful tool for generating novel biological insights from the growing Human Cell Atlas.