bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverse Configurations of Erroneous Predictive Coding Across Brain Hierarchies in a Non-Human Primate Model of Autism Spectrum Disorder
Authors: Chao Zenas C. , Komatsu Misako , Matsumoto Madoka , Iijima Kazuki , Nakagaki Keiko , Ichinohe Noritaka 
Published: November 2023

AbstractIn autism spectrum disorder (ASD), atypical sensory experiences are often associated with irregularities in predictive coding, which proposes that the brain creates hierarchical sensory models via a bidirectional process of predictions and prediction errors. However, it remains unclear how these irregularities manifest across different functional hierarchies in the brain. To address this, we used high-density electrocorticography (ECoG) in a non-human primate model of ASD during an auditory task with two layers of temporal control, and applied a quantitative model to quantify the integrity of predictive coding across two distinct hierarchies. Our results demonstrate that ASD is characterized by sensory hypersensitivity and unstable predictions across two brain hierarchies, and reveal the associated spatio-spectro-temporal neural signatures. Importantly, we observe diverse configurations of underestimation or overestimation of sensory regularities within these hierarchies. This work provides a multi-layered biomarker for ASD, contributing to our understanding of its diverse symptoms.
Rhizonet: Image Segmentation for Plant Root in Hydroponic Ecosystem
Authors: Ushizima Daniela , Sordo Zineb , Andeer Peter , Sethian James , Northen Trent 
Published: November 2023

ABSTRACTDigital cameras have the ability to capture daily images of plant roots, allowing for the estimation of root biomass. However, the complexities of root structures and noisy image backgrounds pose challenges for advanced phenotyping. Manual segmentation methods are laborious and prone to errors, which hinders experiments involving several plants. This paper introduces Rhizonet, a supervised deep learning approach for semantic segmentation of plant root images. Rhizonet harnesses a Residual U-Net backbone to enhance prediction accuracy, incorporating a convex hull operation to precisely outline the largest connected component. The primary objective is to accurately segment the biomass of the roots and analyze their growth over time. The input data comprises color images of various plant samples within a hydroponic environment known as EcoFAB, subject to specific nutrition treatments. Validation tests demonstrate the robust generalization of the model across experiments. This research pioneers advances in root segmentation and phenotype analysis by standardizing processes and facilitating the analysis of thousands of images while reducing subjectivity. The proposed root segmentation algorithms contribute significantly to the precise assessment of the dynamics of root growth under diverse plant conditions.
A novel thin plate spline methodology to model tissue surfaces and quantify tumor cell invasion in organ-on-chip models
Authors: Elton Elizabeth , Strelez Carly , Ung Nolan , Perez Rachel , Ghaffarian Kimya , Matasci Naim , Mumenthaler Shannon M. 
Published: November 2023

ABSTRACTOrgan-on-chip (OOC) models can be useful tools for cancer drug discovery. Advances in OOC technology have led to the development of more complex assays, yet analysis of these systems does not always account for these advancements, resulting in technical challenges. A challenging task in the analysis of these two-channel microfluidic models is to define the boundary between the channels so objects moving within and between channels can be quantified. We propose a novel imaging-based application of a thin plate spline method – a generalized cubic spline that can be used to model coordinate transformations – to model a tissue boundary and define compartments for quantification of invaded objects, representing the early steps in cancer metastasis. To evaluate its performance, we applied our analytical approach to an adapted OOC developed by Emulate, Inc., utilizing a two-channel system with endothelial cells in the bottom channel and colorectal cancer (CRC) patient-derived organoids (PDOs) in the top channel. Initial application and visualization of this method revealed boundary variations due to microscope stage tilt and ridge and valley-like contours in the endothelial tissue surface. The method was functionalized into a reproducible analytical process and web tool – the Chip Invasion and Contour Analysis (ChICA) – to model the endothelial surface and quantify invading tumor cells across multiple chips. To illustrate applicability of the analytical method, we applied the tool to CRC organoid-chips seeded with two different endothelial cell types and measured distinct variations in endothelial surfaces and tumor cell invasion dynamics. Since ChICA utilizes only positional data output from imaging software, the method is applicable to and agnostic of the imaging tool and image analysis system used. The novel thin plate spline method developed in ChICA can account for variation introduced in OOC manufacturing or during the experimental workflow, can quickly and accurately measure tumor cell invasion, and can be used to explore biological mechanisms in drug discovery.
Anticipation of sexually arousing visual event leads to overestimation of elapsed time
Authors: Harjunen Ville Johannes , Spapé Michiel , Ravaja Niklas 
Published: November 2023

AbstractSubjective estimates of duration are affected by emotional expectations about the future. For example, temporal intervals preceding a threatening event such as an electric shock are estimated as longer than intervals preceding a non-threatening event. However, it has not been unequivocally shown that such temporal overestimation occurs also when anticipating a similarly arousing but appealing event. In this study, we examined how anticipation of visual erotic material influenced perceived duration. Participants did a temporal bisection task, where they estimated durations of visual cues relative to previously learned short and long standard durations. The colour of the to-be-timed visual cue signalled either a chance of seeing a preferred erotic picture at the end of the interval or certainty of seeing a neutral grey bar instead. The results showed that anticipating an appealing event increased the likelihood of estimating the cue duration as long as compared to the anticipation of a grey bar. Further analyses showed that this temporal overestimation effect was stronger for those who rated the anticipated erotic pictures as more sexually arousing. The results thus indicate that anticipation of appealing events has a similar dilating effect on perceived duration as does the anticipation of aversive events.
The Expression of HIV-1 Tat inLactococcus lactis
Authors: Selvam Deepak , D’silva Anish , Gohil Yuvraj , singh Jayendra , Panchapakesan Arun , Hanna Luke Elizabeth , Ranga Udaykumar 
Published: November 2023

AbstractEfficient expression of functional proteins in heterologous hosts has become the pivotal focus of modern biotechnology and biomedical research. To this end, multiple alternatives toE. coliare being explored for recombinant protein expression.L. lactis, being a gram-positive organism, circumvents the need for an endotoxin removal step during protein purification. We report here the optimisation of the expression of HIV-1 Tat, a notoriously difficult protein, inLactococcus lactissystem. We evaluated five different promoters in two differentLactococcus lactisstrains and examined the effect of pH, glucose, and induction time on the yield and purity of Tat. Finally, the recombinant Tat was functionally competent in transactivating the HIV-1 promoter in HLM-1 reporter cells. Our work provides a scaffold for future work on the expression of toxic proteins inLactococcus lactis.
High-resolution structure of a replication-initiation like configuration of influenza polymerase active site visualises the essential role of a conserved dibasic motif in the PA subunit
Authors: Drncova Petra , Krischuns Tim , Naffakh Nadia , Cusack Stephen 
Published: November 2023

AbstractInfluenza polymerase, comprising subunits PA, PB1 and PB2, transcribes the negative-sense genomic viral RNA (vRNA) into mRNA or replicates it first into complementary RNA (cRNA) and then back to vRNA. Here we investigate the mechanism ofde novo(unprimed) initiation of vRNA to cRNA replication. We present a high-resolution structure of A/little-yellow-shouldered-bat/H17N10 polymerase with the 3’ end of the template in the RNA synthesis active site, both in the apo-state and after soaking with GTP and CTP. The priming GTP and incoming CTP are observed to base-pair to template nucleotides C2 and G3 at the -1 and +1 positions respectively, thus representing a replication initiation-like state. This configuration is stabilised by partial stacking of the tip of the priming loop on the GTP:C2 base-pair and the interaction of PB1/H649 and dibasic motif residues PA/R658 and K659 with the triphosphate of the priming GTP. The dibasic motif is universally conserved in orthomyxovirus PA subunits. Trans-complementation assays in cells using mutants of PA/K659 show that the dibasic motif is specifically essential for replication. These results shed light on the mechanism of replication initiation even though vRNA to cRNA replication is expected to be terminally initiated, with priming ATP and incoming GTP base-pairing to template nucleotides U1 and C2 at the -1 and +1 positions respectively, implying a different position of the template.
The staphylococcal type VII secretion system impacts daptomycin sensitivity through controlling bacterial cell envelope integrity
Authors: Smith Victoria , Chandrasekharan Giridhar , Watkins Kate E. , Marset Ramon Garcia , Yap Jeannifer , Perrier Sebastien , Tchoupa Arnaud Kengmo , Unnikrishnan Meera 
Published: November 2023

SummaryTheStaphylococcus aureustype VII secretion system (T7SS) plays an important role in bacterial virulence during infection. However, T7SS functions during infection and in bacterial physiology are poorly understood. Here, we demonstrate thatS. aureusstrains lacking the T7SS transporter EssC or effectors, EsxC and EsxA, were highly sensitive to the important last resort drug, daptomycin. T7SS mutants displayed decreased membrane fluidity, altered cell membrane protein localisation, distinct cell surface morphologies, with effects on cell wall synthesis as well as surface charge under normal growth conditions, indicating that the T7SS is critical to cell envelope function. Daptomycin binding was enhanced in the mutants, whose membranes were more permeable when treated with the drug. Furthermore, the lack of EsxC enhanced daptomycin sensitivity during intracellular infection and during murine skin infection. Thus, our data show that the staphylococcal T7SS impacts sensitivity to membrane-acting drugs through modulating membrane integrity, indicating its potential as a drug target.
CEP44 is required for maintaining centriole duplication and spindle integrity
Authors: Zhang Donghui , Wei Wenlu , Zou Xiaopeng , Meng Hui , Li Fangyuan , Yao Minjun , Teng Junling , Huang Ning , Chen Jianguo 
Published: November 2023

AbstractIn animal cells, the centrosome, consisting of two centrioles, duplicates only once per cell cycle for bipolar spindle formation. Defective centriole duplication results in abnormal spindle formation and chromosome missegregation, which is closely linked to tumor growth. However, the molecular mechanisms licensing only one centriole duplication cycle within a cell cycle are less well known. Here we found that CEP44 is negatively correlated with breast carcinoma. CEP44, jointly with CEP57 and CEP57L1, maintains centriole engagement in the interphase to ensure centriole duplication once per cell cycle. Depletion of CEP44 leads to centriole overduplication because of premature centriole disengagement, and multipolar spindle formation. Additionally, CEP44 is phosphorylated by Aurora A at the G2/M phase to facilitate spindle localization and maintain spindle integrity. Collectively, our results show the function of CEP44 in spindle formation by preventing centriole overduplication and maintaining spindle integrity, and CEP44 may serve as a potential marker for breast carcinoma prognosis.
Metagenome profiling and containment estimation through abundance-corrected k-mer sketching with sylph
Authors: Shaw Jim , Yu Yun William 
Published: November 2023

AbstractProfiling metagenomes against databases allows for the detection and quantification of mi-crobes, even at low abundances where assembly is not possible. We introduce sylph (https://github.com/bluenote-1577/sylph), a metagenome profiler that estimates genome-to-metagenome containment average nucleotide identity (ANI) through zero-inflated Poisson k-mer statistics, enabling ANI-based taxa detection. Sylph is the most accurate method on the CAMI2 marine dataset, and compared to Kraken2 for multi-sample profiling, sylph takes 10× less CPU time and uses 30× less memory. Sylph’s ANI estimates provide an orthogonal signal to abundance, enabling an ANI-based metagenome-wide association study for Parkinson’s disease (PD) against 289,232 genomes while confirming known butyrate-PD associations at the strain level. Sylph takes < 1 minute and 16 GB of RAM to profile against 85,205 prokaryotic and 2,917,521 viral genomes, detecting 30× more viral sequences in the human gut compared to RefSeq. Sylph offers precise, efficient profiling with accurate containment ANI estimation for even low-coverage genomes.
YeastIT: Reducing mutational bias for in vivo directed evolution using a novel yeast mutator strain based on dual adenine-/cytosine-targeting and error-prone DNA repair
Authors: Napiorkowska Marta , Fischer Katrin , Penner Matthew , Knyphausen Philipp , Hollfelder F. 
Published: November 2023

AbstractEngineering proteins with new functions and properties often requires navigating large sequence spaces through rounds of iterative improvement. However, a disparity exists between the gradual pace of natural long-term evolution and a typical laboratory evolution workflow that relies on enriching functional variants from highly diverse in vitro generated libraries through very few screening rounds. Laboratory experiments often eschew presumed natural strategies such as neutral/non-adaptive and multi-phase evolution trajectories, and therefore mutagenesis technologies suitable for long ‘nature-like’ timescales are needed. Here, we introduce YeastIT, a novel in vivo mutagenesis tool for protein engineering that leverages anS. cerevisiaestrain engineered to exhibit mutagenic activity directed to the gene of interest, allowing its continuous diversification. Mutagenesis is achieved by generating DNA damage through nucleoside deamination, followed by introduction of mutations by harnessing the process of error-prone DNA translesion synthesis. By eliminating the transformation step, YeastIT allows multiple rounds of screening or selection without interruptions for library diversification, thereby enabling long-term and continuous evolution campaigns. Our characterization of the mutational spectrum and frequency of the YeastIT-generated libraries, and its comparison to other methods (error-prone PCR, PACE, MutaT7, eMutaT7, OrthoRep, TRIDENT, EvolVR) demonstrates comparable mutation rates combined with a significant reduction in mutagenic bias relative to most of the alternatives. To validate YeastIT, we carried out directed evolution of a DARPin binding protein to achieve a 15-fold improved affinity. YeastIT thus provides a tool for exploring different evolutionary trajectories which overcomes previous limitations of variant availability (due to bias and low mutation rates) and emulates the way proteins emerge in Nature.
A novel highly divergent enteric calicivirus in a bovine calf, India
Authors: Kumar Naveen , Kaushik Rahul , Yadav Pragya , Sircar Shubhankar , Shete-Aich Anita , Singh Ashutosh , Malik Yashpal Singh 
Published: November 2023

AbstractIn 2015, a novel highly divergent bovine calicivirus was detected in an Indian calf with enteritis. Phylogenetic analysis linked it to theNeboviruswith only 38.5% sequence identities, emphasizing the need for separate taxonomic classification. Furthermore, PCR screening detected these unique caliciviruses widely in India’s northern states.
Designer antisense circRNAGFPreduces GFP protein abundance in transgenic Arabidopsis protoplasts in a sequence-specific manner, independent of RNAi pathways
Authors: Hossain M , Pfafenrot C , Imani J , Šečić E , Sede A , Galli M , Heinlein M , Bindereif A , Ladera-Carmona M , Kogel KH 
Published: November 2023

AbstractCircular RNAs (circRNAs) are single-stranded molecules that have attracted increasing attention in recent years due to their covalently closed structure and their diverse functional roles in mammalian cells, where they are involved in the regulation of gene expression and protein function. Increasing evidence suggests that circRNAs have similar functions in plants, where they play a role in plant development, resistance to biotic stress, and abiotic stress tolerance. Here, we investigated the agronomically relevant question of whether synthetic designer circRNAs can be used to modulate in a sequence-specific manner gene expression in plants. We show that treatment ofGFP-expressing Arabidopsis protoplasts with designer 50 nt GFP antisense circRNA (circRNAGFP) reduces the cellular accumulation of the reporter protein in a sequence-specific and dose-dependent manner. This inhibitory activity of circRNAGFPwas not abolished in various Arabidopsisagoanddclmutants with defective RNAi pathways. Moreover, and in contrast to other types of RNA such as double-stranded (ds)RNA, circRNAs did not induce a PTI response in plant leaves. We discuss the possibility that circRNA may be applied to regulate endogenous plant genes and thus may have future potential as a novel bioherbicide.
SmCCNet 2.0: A Comprehensive Tool for Multi-omics Network Inference with Shiny Visualization
Authors: Liu Weixuan , Vu Thao , Konigsberg Iain , Pratte Katherine , Zhuang Yonghua , Kechris Katerina 
Published: November 2023

AbstractSummarySparse multiple canonical correlation network analysis (SmCCNet) is a machine learning technique for integrating omics data along with a variable of interest (e.g., phenotype of complex disease), and reconstructing multi-omics networks that are specific to this variable. We present the second-generation SmCCNet (SmCCNet 2.0) that adeptly integrates single or multiple omics data types along with a quantitative or binary phenotype of interest. In addition, this new package offers a streamlined setup process that can be configured manually or automatically, ensuring a flexible and user-friendly experience.AvailabilityThis package is available in both CRAN:https://cran.r-project.org/web/packages/SmCCNet/index.htmland Github:https://github.com/KechrisLab/SmCCNetunder the MIT license. The network visualization tool is available athttps://smccnet.shinyapps.io/smccnetnetwork/.
Molecular regulation of retinal regeneration is context specific
Authors: Emmerich Kevin , Hageter John , Hoang Thanh , Lyu Pin , Sharrock Abigail V. , Ceisel Anneliese , Thierer James , Chunawala Zeeshaan , Nimmagadda Saumya , Palazzo Isabella , Matthews Frazer , Zhang Liyun , White David T. , Rodriquez Catalina , Graziano Gianna , Marcos Patrick , May Adam , Mulligan Tim , Reibman Barak , Saxena Meera T. , Ackerley David F. , Qian Jiang , Blackshaw Seth , Horstick Eric , Mumm Jeff S. 
Published: November 2023

AbstractMany genes are known to regulate retinal regeneration following widespread tissue damage. Conversely, genes controlling regeneration following limited retinal cell loss, akin to disease conditions, are undefined. Combining a novel retinal ganglion cell (RGC) ablation-based glaucoma model, single cell omics, and rapid CRISPR/Cas9-based knockout methods to screen 100 genes, we identified 18 effectors of RGC regeneration kinetics. Surprisingly, 32 of 33 previously known/implicated regulators of retinal tissue regeneration were not required for RGC replacement; 7 knockouts accelerated regeneration, includingsox2, olig2,andascl1a. Mechanistic analyses revealed loss ofascl1aincreased “fate bias”, the propensity of progenitors to produce RGCs. These data demonstrate plasticity and context-specificity in how genes function to control regeneration, insights that could help to advance disease-tailored therapeutics for replacing lost retinal cells.One sentence summaryWe discovered eighteen genes that regulate the regeneration of retinal ganglion cells in zebrafish.
Behavioral and neuropathological features of Alzheimer’s disease are attenuated in 5xFAD mice treated with intranasal GHK peptide
Authors: Tucker Matthew , Liao Gerald Yu , Park Joo Young , Rosenfeld Manuela , Wezeman Jackson , Mangalindan Ruby , Ratner Dan , Darvas Martin , Ladiges Warren 
Published: November 2023

AbstractEfforts to find disease modifying treatments for Alzheimer’s disease (AD) have met with limited success in part because the focus has been on testing drugs that target a specific pathogenic mechanism. Multiple pathways have been implicated in the pathogenesis of AD. Hence, the probability of more effective treatment for AD is likely increased by using an intervention that targets more than one pathway. The naturally occurring peptide GHK (glycyl-L-histidyl-L-lysine), as a GHK-Cu complex, supports angiogenesis, remodeling, and tissue repair, has anti-inflammatory and antioxidant properties, and has been shown to improve cognitive performance in aging mice. In order to test GHK-Cu as a neurotherapeutic for AD, male and female 5xFAD transgenic mice on the C57BL/6 background at 4 months of age were given 15 mg/kg GHK-Cu intranasally 3 times per week for 3 months until 7 months of age. Results showed that intranasal GHK-Cu treatment delayed cognitive impairment, reduced amyloid plaques, and lowered inflammation levels in the frontal cortex and hippocampus. These observations suggest additional studies are warranted to investigate the potential of GHK-Cu peptide as a promising treatment for AD.