bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of inhibitory peptides againstE. coliwith desired MIC value
Authors: Bajiya Nisha , Kumar Nishant , Raghava Gajendra P. S. 
Published: July 2024

AbstractIn the past, several methods have been developed for predicting antibacterial and antimicrobial peptides, but only limited attempts have been made to predict their minimum inhibitory concentration (MIC) values. In this study, we trained our models on 3,143 peptides and validated them on 786 peptides whose MIC values have been determined experimentally againstEscherichia coli(E. coli). The correlational analysis reveals that the Composition Enhanced Transition and Distribution (CeTD) attributes strongly correlate with MIC values. We initially employed the similarity search strategy utilizing BLAST to estimate MIC values of peptides but found it inadequate for prediction. Next, we developed machine learning techniques-based regression models using a wide range of features, including peptide composition, binary profile, and embeddings of large language models. We implemented feature selection techniques like minimum Redundancy Maximum Relevance (mRMR) to select the best relevant features for developing prediction models. Our Random forest-based regressor, based on selected features, achieved a correlation coefficient (R) of 0.78, R-squared (R²) of 0.59, and a root mean squared error (RMSE) of 0.53 on the validation dataset. Our best model outperforms the existing methods when benchmarked on an independent dataset of 498 inhibitory peptides ofE. coli. One of the major features of the web-based platform EIPpred developed in this study is that it allows users to identify or design peptides that can inhibitE. coliwith the desired MIC value (https://webs.iiitd.edu.in/raghava/eippred).HighlightsPrediction of MIC value of peptides againstE.coli.An independent dataset was generated for comparison.Feature selection using the mRMR method.A regressor method for designing novel inhibitory peptides.A web server and standalone package for predicting the inhibitory activity of peptides.
CODARFE: Unlocking the prediction of continuous environmental variables based on microbiome
Authors: Barbosa Murilo Caminotto , da Silva João Fernando Marques , Alves Leonardo Cardoso , Finn Robert D , Paschoal Alexandre Rossi 
Published: July 2024

AbstractDespite the surge in data acquisition, there is a limited availability of tools capable of effectively analyzing microbiome data that identify correlations between taxonomic compositions and continuous environmental factors. Furthermore, existing tools also do not predict the environmental factors in new samples, underscoring the pressing need for innovative solutions to enhance our understanding of microbiome dynamics and fulfill the prediction gap. Here, we introduce CODARFE, a novel tool for sparse compositional microbiome-predictors selection and prediction of continuous environmental factors. We tested CODARFE against four state-of-the-art tools in two experiments. First, CODARFE outperformed predictor selection in 21 out of 24 databases in terms of correlation. Second, among all the tools, CODARFE achieved the highest number of previously identified bacteria linked to environmental factors for human data—that is, at least 7% more. We also tested CODARFE in a cross-study, using the same biome but under different external effects (e.g., ginseng field and cattle for arable soil, and HIV and crohn’s disease for human gut), using a model trained on one dataset to predict environmental factors on another dataset, achieving 11% of mean absolute percentage error. Finally, CODARFE is available in five formats, including a Windows version with a graphical interface, to installable source code for Linux servers and an embedded Jupyter notebook available at MGnify -https://github.com/alerpaschoal/CODARFE.
The dynamic and diverse nature of parenchyma cells in the Arabidopsis root during secondary growth
Authors: Lyu Munan , Iida Hiroyuki , Eekhout Thomas , Mäkelä Meeri , Muranen Sampo , Ye Lingling , Vatén Anne , Wybouw Brecht , Wang Xin , De Rybel Bert , Mähönen Ari Pekka 
Published: July 2024

AbstractDuring the process of secondary growth, the vascular cambium produces the conductive xylem and phloem cells, while the phellogen (cork cambium) deposit phellem (cork) as the outermost protective barrier. Although most of the secondary tissues is made up by parenchyma cells which are also produced by both cambia, their diversity and function are poorly understood. Here we combined single-cell RNA sequencing analysis with lineage tracing to recreate developmental trajectories of the cell types in theArabidopsisroot undergoing secondary growth. By analysing 93 reporter lines, we were able to identify 20 different cell types or cell states, many of which have not been described before. We additionally observed distinct transcriptome signatures of parenchyma cells depending on their maturation state and proximity to the conductive cell types. Our data shows that both xylem and phloem parenchyma tissues are required for normal formation of conductive tissue cell types. Furthermore, we showed that mature phloem parenchyma gradually obtains periderm identity, and this transition can be accelerated by jasmonate or wounding. Thus, our study reveals the remarkable dynamic and diverse nature of parenchyma cells during secondary growth.
Embryo movement is required for limb tendon maturation
Authors: Rolfe Rebecca A. , Talak Busturkmen Ebru , Sliney Lauren , Hayden Grace , Dunne Nicholas , Buckley Niamh , McCarthy Helen , Szczesny Spencer E. , Murphy Paula 
Published: July 2024

AbstractFollowing early cell specification and tenocyte differentiation at the sites of future tendons, very little is known about how tendon maturation into robust load-bearing tissue is regulated. Between embryonic day (E)16 and E18 in the chick, there is a rapid change in mechanical properties which is dependent on normal embryo movement. However, the tissue, cellular and molecular changes that contribute to this transition are not well defined. Here we profiled aspects of late tendon development (collagen fibre alignment, cell organisation and Yap pathway activity), describing changes that coincide with tissue maturation. We compared effects of rigid (constant static loading) and flaccid (no loading) immobilisation to gain insight into developmental steps influenced by mechanical cues. We show that YAP signalling is active and responsive to movement in late tendon. Collagen fibre alignment increased over time and under static loading. Cells organise into end-to-end stacked columns with increased distance between adjacent columns, where collagen fibres are deposited; this organisation was lost following both types of immobilisation. We conclude that specific aspects of tendon maturation requires controlled levels of dynamic muscle-generated stimulation. Such a developmental approach to understanding how tendons are constructed will inform future work to engineer improved tensile load-bearing tissues.
Discrimination of Jamaican fruit bat lymphocytes by flow cytometry
Authors: Burke Bradly E. , Rocha Savannah M. , Campbell Corey , Creissen Elizabeth , Tjalkens Ronald B. , Ma Wenjun , Henao-Tamayo Marcela , Schountz Tony 
Published: July 2024

AbstractBats are natural reservoir hosts of many important zoonotic viruses but because there are few immunological reagents and breeding colonies available for infectious disease research, little is known about their immune responses to infection. We established a breeding colony Jamaican fruit bats (Artibeus jamaicensis) to study bat virology and immunology. The species is used as a natural reservoir model for H18N11 influenza A virus, and as a surrogate model for SARS-CoV-2, MERS-CoV and Tacaribe virus. As part of our ongoing efforts to develop this model organism, we sought to identify commercially available monoclonal antibodies (mAb) for profiling Jamaican fruit bat lymphocytes. We identified several cross-reactive mAb that can be used to identify T and B cells; however, we were unable to identify mAb for three informative T cell markers, CD3γ, CD4 and CD8α. We targeted these markers for the generation of hybridomas, and identified several clones to each that can be used with flow cytometry and fluorescence microscopy. Specificity of the monoclonal antibodies was validated by sorting lymphocytes, followed by PCR identification of confirmatory transcripts. Spleens of Jamaican fruit bats possess about half the number of T cells than do human or mouse spleens, and we identified an unusual population of cells that expressed the B cell marker CD19 and the T cell marker CD3. The availability of these monoclonal antibodies will permit a more thorough examination of adaptive immune responses in Jamaican fruit bats that should help clarify how the bats control viral infections and without disease.ImportanceBats naturally host a number of viruses without disease, but which can cause significant disease in humans. Virtually nothing is known about adaptive immune responses in bats because of a lack of immunological tools to examine such responses. We have begun to address this deficiency by identifying several commercially available monoclonal antibodies to human and mouse antigens that are cross-reactive to Jamaican fruit bat lymphocyte orthologs. We also generated monoclonal antibodies to Jamaican fruit bat CD3γ, CD4 and CD8α that are suitable for identifying T cell subsets by flow cytometry and immunofluorescent staining of fixed tissues. Together, these reagents will allow a more detailed examination of lymphocyte populations in Jamaican fruit bats.
Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration
Authors: Lv Guohua , Sayles Nicole M. , Huang Yun , Mancinelli Chiara D. , McAvoy Kevin , Shneider Neil A. , Manfredi Giovanni , Kawamata Hibiki , Eliezer David 
Published: July 2024

AbstractCHCHD10 is mutated in rare cases of FTD and ALS and aggregates in mouse models of disease. Here we show that the disordered N-terminal domain of CHCHD10 forms amyloid fibrils and report their cryoEM structure. Disease-associated mutations cannot be accommodated by the WT fibril structure, while sequence differences between CHCHD10 and CHCHD2 are tolerated, explaining the co-aggregation of the two proteins and linking CHCHD10 and CHCHD2 amyloid fibrils to neurodegeneration.
Preventing escape and malfunction of recoded cells due to tRNA base changes
Authors: Chiappino-Pepe Anush , Radford Felix , Budnik Bogdan , Taş Hüseyin , Augustin Teresa L , Burgess Hana M , Moret Michaël , Dharani Azim M , Zheng Qinmei , Fan Weicheng , Africawala Maksud M , Thapa Shova , Kuru Erkin , Narasimhan Kamesh , Marchand Jorge A , Perrotta Ramiro M , Stokes Jonathan M , Lunshof Jeantine E , Aach John D , Tam Jenny M , Church George M 
Published: July 2024

AbstractEngineering the genetic code restricts DNA transfer (cellular bioisolation) and enables new chemistries via non-standard amino acid incorporation. These distinct properties make recoded cells state-of-the-art safe technologies. However, evolutionary pressures may endanger the longevity of the recoding. Here, we reveal that recodedEscherichia colilacking 18,214 serine codons and two tRNASercan express wild-type antibiotic resistance genes and escape up to seven orders of magnitude faster than expected. We show a two-step escape process whereby recoded cells mistranslate antibiotic resistance genes to survive until modified or mutated tRNAs reintroduce serine into unassigned codons. We developed genetic-code-sensitive kill switches that sense serine incorporation and prevent cellular escape while preserving encoding of three distinct non-standard amino acids. This work lays the foundation for the long-term controlled function of cells that incorporate new chemistries, with implications for the design, use, and biosafety of synthetic genomes in clinical and environmental applications where physical containment is insufficient.
Early evolution of BA.2.86 sheds light on the origins of highly divergent SARS-CoV-2 lineages
Authors: Escalera-Zamudio Marina , Tan Cedric C S , van Dorp Lucy , Balloux François 
Published: July 2024

ABSTRACTSince the emergence of SARS-CoV-2 in late 2019, highly divergent variants with novel constellations of mutations have periodically emerged to displace previously co-circulating virus lineages. The evolutionary mechanisms behind this process remain unclear, but the prevailing hypothesis supports emergence through single events followed by a rapid accumulation of mutations in individual long-term infections. In July 2023, the Omicron-descending BA.2.86 Variant of Interest (VOI) emerged to outcompete other virus lineages, with descending sublineages still dominating as of December 2024. We use BA.2.86 as a case study to test the hypothesis that highly divergent variants emerge during a single chronic infection. By applying a comprehensive suite of evolutionary analyses to independent high-resolution datasets, we identify a cluster of approximately 100 BA.2 genomes that fall directly ancestral and shorten the branch leading to BA.2.86, carrying some BA.2.86-specific lineage defining mutations. These genomes, sampled from multiple countries and at different timepoints, share a single ancestor dating back to December 2021. Additionally, we detect over 2600 earlier BA.2, BA.2.75, and XBB.1.5 genomes with multiple mutations later associated with BA.2.86. These genomes represent a standing genetic variation that likely facilitated a gradual evolution in the direct ancestry of this variant. We further uncover a complex evolutionary process involving recombination between the BA.2.75 and XBB.1.5 parental lineages. Together, our results challenge the notion of a single emergence event, and instead support a more complex scenario, with BA.2.86 likely having evolved over multiple transmission chains.
Rapid Detection of Active Coronavirus Infection by Lateral Flow Test Strips: A New Approach to Distinguish Replicating Viruses from Non-Replicating Viruses
Authors: Davis Darnell , Lamb Caitlin H. , Myhrvold Cameron , Ullah Hemayet 
Published: July 2024

AbstractThis manuscript describes the development of an alternative method to detect active coronavirus infection, which targets negative-sense RNA, a product of active viral replication. Few diagnostic methods are capable of discriminating between replicating and non-replicating viruses, complicating decisions related to quarantine and therapeutic interventions. We propose strand-specific nucleic acid diagnostics as a means of distinguishing between active and inactive RNA virus infections and prototype a CRISPR-based lateral flow assay that specifically detects replicating coronaviruses. Such a paradigm in diagnostics could guide more effective public health measures to curb the spread of SARS-CoV-2 and other single-stranded viruses.
The impacts of viral interaction on household transmission of respiratory viruses
Authors: Ibiebele Jessica C. , Godonou Elie-Tino , Callear Amy P. , Smith Matthew R. , Truscon Rachel , Johnson Emileigh , Eisenberg Marisa C. , Lauring Adam S. , Monto Arnold S. , Cobey Sarah , Martin Emily T. 
Published: July 2024

AbstractThe possibility of virus-virus interaction has been hypothesized at the population level, but there are limited data regarding the effects of viral interaction on transmission. This study used data from a prospective household cohort study to examine how viral interaction impacts transmission of influenza A virus (IAV), influenza B virus (IBV), and respiratory syncytial virus (RSV). We used two main predictors of transmission: coinfection in the index case and detection of a virus other than a primary virus of interest in the susceptible contact. Household- and individual-level analyses were conducted for IAV, IBV, and RSV. To estimate the risk of transmission within households with coinfected index cases, a household-level analysis was performed using multivariable regression with Poisson mixed effects models. To estimate an individual’s risk of transmission when multiple viruses co-circulated within their household, an individual-level analysis was performed using mixed-effects logistic regression models. Coinfection among index cases was associated with reduced transmission of IAV and RSV. Infection with a different virus among household contacts was associated with an increased risk of transmission of IAV and RSV. This study enhances the understanding of viral interaction by elucidating the potential impacts of interaction on virus transmission. These findings could have important implications for public health planning and prevention efforts.
The RpfB switch is a novel B12-sensing riboswitch regulating (non-replicating) persistence inMycobacterium tuberculosis
Authors: Kipkorir Terry , Polgar Peter , D’Halluin Alexandre , Gap-Gaupool Brindha , Makarov Vadim A. , Mukamolova Galina V. , Arnvig Kristine B. 
Published: July 2024

AbstractRiboswitches are metabolite-sensing RNA elements that control a wide range of genes in bacteria. Most riboswitches identified to date are broadly conserved and control genes that are directly involved in the transport or biosynthesis of their cognate ligands. However, a minority of switches are restricted to a few species and in addition may bind less obvious ligands. One such switch controls the expression of theMycobacterium tuberculosis rpfBoperon, which is critical for resuscitation of dormant bacteria, ribosome maturation and reactivation of latent tuberculosis infection. The switch is restricted to pathogenic mycobacteria and until now, its ligand was unknown. However, in the current study, we identify the ligand as cobalamin or vitamin B12. Using in-line probing, we show that vitamin B12binds directly to the riboswitch RNA, and we predict a structure based on the cleavage pattern. Moreover, we show that B12suppresses the expression of anrpfB-lacZreporter fusion and crucially, that B12suppresses resuscitation ofM. tuberculosisfrom a state of non-replicating persistence. These findings demonstrate a pivotal role of crosstalk between a host-derived metabolite and a pathogen riboswitch in controllingM. tuberculosispersistence with potential for improved interventions.
The noncoding circular RNAcircHomer1regulates synaptic development and experience-dependent plasticity in mouse visual cortex
Authors: Jenks Kyle R. , Cai Ying , Nayan Marvin Eduarte , Tsimring Katya , Li Keji , Zepeda José C. , Heller Gregg R. , Delepine Chloe , Shih Jennifer , Yuan Shiyang , Zhu Yao , Wang Ye , Duan Yangyang , Fu Amy K. Y. , Ku Taeyun , Yun Dae Hee , Chung Kwanghun , Mellios Nikolaos , Sur Mriganka , Ip Jacque Pak Kan 
Published: July 2024

AbstractCircular RNAs (circRNAs) are a class of closed-loop, single stranded RNAs whose expression is particularly enriched in the brain. Despite this enrichment and evidence that the expression of circRNAs are altered by synaptic development and in response to synaptic plasticityin vitro, the regulation by and function of the majority of circRNAs in experience-dependent plasticityin vivoremain unexplored. Here, we employed transcriptome-wide analysis comparing differential expression of both mRNAs and circRNAs in juvenile mouse primary visual cortex (V1) following monocular deprivation (MD), a model of experience-dependent developmental plasticity. Among the differentially expressed mRNAs and circRNAs following 3-day MD, the circular and the activity-dependent mRNA forms of theHomer1gene,circHomer1andHomer1arespectively, were of interest as their expression changed in opposite directions:circHomer1expression increased while the expression ofHomer1adecreased following 3-day MD. Knockdown ofcircHomer1delayed the depression of closed-eye responses normally observed after 3-day MD.circHomer1-knockdown also led to a reduction in average dendritic spine size prior to MD but critically there was no further reduction after 3-day MD, consistent with impaired structural plasticity.circHomer1-knockdown also prevented the reduction of surface AMPA receptors after 3-day MD. Synapse-localized puncta of the AMPA receptor endocytic protein Arc increased in volume after MD but were smaller incircHomer1-knockdown neurons, suggesting thatcircHomer1knockdown impairs experience-dependent AMPA receptor endocytosis. Thus, the expression of multiple circRNAs are regulated by experience-dependent developmental plasticity, and our findings highlight the essential role ofcircHomer1in V1 synaptic development and experience-dependent plasticity.Significance StatementCircular RNAs (circRNAs) are a class of closed-loop RNAs formed through back-splicing of exon and/or intron junctions. Initially considered as byproducts of aberrant RNA splicing with limited function, recent studies have implicated circRNAs in various neurological disorders. Despite their abundant expression in the brain, the role of circRNAs in experience-dependent plasticity remains poorly understood. We conducted anin vivotranscriptome analysis of circRNAs whose expression was regulated by experience-dependent plasticity in the mouse visual cortex and highlightcircHomer1, a circRNA derived from theHomer1gene, as a circRNA critical for synaptic development and experience-dependent plasticityin vivo.
Extracts of food and medicinal plants sold in Moroccan markets induce apoptosis-like inToxoplasma gondiitachyzoitesin vitro
Authors: Elkoraichi Ismail , Moiré Nathalie , Rais Samira , Dimier-Poisson Isabelle , Daoudi Fouad , Debierre-Grockiego Françoise 
Published: July 2024

AbstractTreatment of congenital toxoplasmosis is potentially toxic and above all too expensive to be administered systematically in middle-income countries such as Morocco. There is therefore a real interest in discovering alternative treatments that would be financially accessible to all. In this context, plants used in traditional medicine and purchased in markets are good candidates. Aqueous extract ofAmmi visnagaseeds had no inhibitory effect againstT. gondiitachyzoites intracellular growthin vitroand induced a cytotoxic effect on host cells. In contrast, ethanolic extract ofA. visnagaseeds showed anti-Toxoplasmaeffect with low cytotoxicity, indicating the compounds extracted differed according to the solvent used. Aqueous extracts ofPunica granatumpeel andSyzygium aromaticumflower buds also showed anti-Toxoplasmaeffect with low cytotoxicity. All the extracts tested, with a greater effect from aqueous and ethanolic extracts ofA. visnagaseeds, induced apoptosis-like of extracellular tachyzoites, as determined by exposure of phosphatidylserine on tachyzoite surface and DNA fragmentation. Finally, the aqueous extracts ofA. visnagaseeds,P. granatumpeel andS. aromaticumflower buds exhibited antioxidant properties. Phytochemical analysis indicated that coumarins and sterols from the aqueous extract ofA. visnaga, saponins from the ethanolic extract ofA. visnaga, gallic tannins from the extract ofP. granatum, and phenols from the extract ofS. aromaticumwere certainly the main components responsible for the different effects observed. The results suggested that the seeds ofA. visnagaand the peel ofP. granatumare the two best candidates for possible preclinical studies on toxoplasmosis.