bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-generation large-scale binary protein interaction network for Drosophila
Authors: Tang Hong-Wen , Spirohn Kerstin , Hu Yanhui , Hao Tong , Kovács István A. , Gao Yue , Binari Richard , Yang-Zhou Donghui , Wan Kenneth H. , Bader Joel S. , Balcha Dawit , Bian Wenting , Booth Benjamin W. , Cote Atina G. , De Rouck Steffi , Desbuleux Alice , Kim Dae-Kyum , Knapp Jennifer J. , Lee Wen Xing , Lemmens Irma , Li Cathleen , Li Mian , Li Roujia , Lim Hyobin Julianne , Luck Katja , Markey Dylan , Pollis Carl , Rangarajan Sudharshan , Rodiger Jonathan , Schlabach Sadie , Shen Yun , TeeKing Bridget , Roth Frederick P. , Tavernier Jan , Calderwood Michael A. , Hill David E. , Celniker Susan E. , Vidal Marc , Perrimon Norbert , Mohr Stephanie E. 
Published: August 2022

AbstractGenerating reference maps of the interactome networks underlying most cellular functions can greatly illuminate genetic studies by providing a protein-centric approach to finding new components of existing pathways, complexes, and processes. Here, we applied state-of-the-art experimental and bioinformatics methods to identify high-confidence binary protein-protein interactions (PPIs) for Drosophila melanogaster. We performed four all-by-all yeast two-hybrid (Y2H) screens of >10,000 Drosophila proteins, resulting in the ‘FlyBi’ dataset of 8,723 PPIs among 2,939 proteins. As part of this effort, we tested subsets of our data and data from previous PPI datasets using an orthogonal assay, which allowed us to normalize data quality across datasets. Next, we integrated our FlyBi data with previous PPI data, resulting in an expanded, high-confidence binary Drosophila reference interaction network, DroRI, comprising 17,232 interactions among 6,511 proteins. These data are accessible through the Molecular Interaction Search Tool (MIST) and other databases. To assess the utility of the PPI resource, we used novel interactions from the FlyBi dataset to generate an autophagy interaction network that we validated in vivo using two different autophagy-related assays. We found that deformed wings (dwg) encodes a protein that is both a regulator and a target of autophagy. Altogether, the resources generated in this project provide a strong foundation for building high-confidence new hypotheses regarding protein networks and function.
Adult and regenerating planarians respond differentially to chronic drug exposure
Authors: Bayingana Kevin , Ireland Danielle , Rosenthal Elizabeth , Rabeler Christina , Collins Eva-Maria S. 
Published: August 2022

AbstractThere is a lack of data on the effects of chronic exposure to common drugs and stimulants on the developing nervous system. Freshwater planarians have emerged as a useful invertebrate model amenable to high-throughput behavioral phenotyping to assay chemical safety in adult and developing brains. Here, we leverage the unique strength of the system to test in parallel for effects on the adult and developing nervous system, by screening ten common drugs and stimulants (forskolin, clenbuterol, LRE-1, MDL-12,330A, adenosine, caffeine, histamine, mianserin, fluoxetine and sertraline) using the asexual freshwater planarianDugesia japonica. The compounds were tested up to 100 µM nominal concentration for their effects on planarian morphology and behavior. Quantitative phenotypic assessments were performed on days 7 and 12 of exposure using an automated screening platform. The antidepressants sertraline and fluoxetine were the most potent to induce lethality, with significant lethality observed at 10 µM. All ten compounds caused sublethal morphological and/or behavioral effects, with the most effects, in terms of potency and breadth of endpoints affected, seen with mianserin and fluoxetine. Four of the compounds (forskolin, clenbuterol, mianserin, and fluoxetine) were developmentally selective, causing effects at lower concentrations in regenerating planarians. Of these, fluoxetine showed the greatest differences between the two developmental stages, inducing many behavioral endpoints in regenerating planarians but only a few in adult planarians. While some of these behavioral effects may be due to neuroefficacy, these results substantiate the need for better evaluation of the safety of these common drugs on the developing nervous system.
Microbial community-based production of single cell protein from soybean-processing wastewater of variable chemical composition
Authors: Vethathirri Ramanujam Srinivasan , Santillan Ezequiel , Thi Sara Swa , Hoon Hui Yi , Wuertz Stefan 
Published: August 2022

AbstractThe use of food-processing wastewaters to produce microbial biomass-derived single cell protein (SCP) is a sustainable way to meet the global food demand. Yet, despite the potential benefits of lower costs and greater resource recovery compared to pure cultures, bioconversion processes relying on microbial community-based approaches to SCP production have received scarce attention. Here, we evaluated SCP production from soybean-processing wastewaters under controlled reactor conditions using the existent microbial communities in these wastewaters. Six sequencing batch reactors of 4.5-L working volume were operated at 30 □ for 34 d in cycles consisting of 3-h anaerobic and 9-h aerobic phases. Four reactors received no microbial inoculum and the remaining two were amended with a 1.5 L of mixed culture from a prior microbial community-based SCP production. Microbial characterization was done via 16S rRNA gene metabarcoding. Influent wastewater batches had variable chemical characteristics but a similar microbial composition. Reactors produced more SCP when fed with wastewaters of higher soluble total Kjeldahl nitrogen (sTKN) content and a lower carbon-to-nitrogen ratio (sCOD:sTKN). The biomass protein yield ranged from 0.24 to 3.13 g protein/g sTKN, with a maximum protein content of 50%. An average of 92% of sCOD and 73% of sTN removal was achieved. Distinct microbial communities were enriched in all six bioreactors after 34 d, where the prevailing genera included Azospirillum, Rhodobacter, Lactococcus, Novosphingobium, and Acidipropionibacterium. In contrast, the microbial community of influent wastewaters was dominated by Lactococcus and Weissella. We showed that constituents in soybean wastewater can be converted to SCP through microbial community-based growth processes and demonstrated the effect of variable influent wastewater composition on SCP production.
Perceptual stability reflected in neuronal pattern similarities in human visual cortex
Authors: Broday-Dvir Rotem , Norman Yitzhak , Harel Michal , Mehta Ashesh D. , Malach Rafael 
Published: August 2022

AbstractThe magnitude of neuronal activation is commonly considered a critical factor for conscious perception of visual content. However, this dogma contrasts with the phenomenon of rapid adaptation, in which the magnitude of neuronal activation drops dramatically in a rapid manner, while the visual stimulus and the conscious experience it elicits remain stable. Here we report that the profiles of multi-site activation patterns and their relational geometry –i.e. the similarity distances between activation patterns, as revealed using iEEG recordings, are sustained during extended stimulation despite the major magnitude decrease. These results are compatible with the hypothesis that conscious perceptual content is associated with the neuronal pattern profiles and their similarity distances, rather than by the overall activation magnitude, in human visual cortex.
Prediction, scanning and designing of TNF-α inducing epitopes for human and mouse
Authors: Dhall Anjali , Patiyal Sumeet , Choudhury Shubham , Jain Shipra , Narang Kashish , Raghava Gajendra P. S. 
Published: August 2022

AbstractTumor Necrosis Factor alpha (TNF-α) is a pleiotropic pro-inflammatory cytokine that plays a crucial role in controlling signaling pathways within the immune cells. Recent studies reported that the higher expression levels of TNF-α is associated with the progression of several diseases including cancers, cytokine release syndrome in COVID-19 and autoimmune disorders. Thus, it is the need of the hour to develop immunotherapies or subunit vaccines to manage TNF-α progression in various disease conditions. In the pilot study, we have proposed a host-specific in-silico tool for the prediction, designing and scanning of TNF-α inducing epitopes. The prediction models were trained and validated on the experimentally validated TNF-α inducing/non-inducing for human and mouse hosts. Firstly, we developed alignment free (machine learning based models using composition of peptides) methods for predicting TNF-α inducing peptides and achieved maximum AUROC of 0.79 and 0.74 for human and mouse hosts, respectively. Secondly, alignment based (using BLAST) method has been used for predicting TNF-α inducing epitopes. Finally, a hybrid method (combination of alignment free and alignment-based method) has been developed for predicting epitopes. Our hybrid method achieved maximum AUROC of 0.83 and 0.77 on an independent dataset for human and mouse hosts, respectively. We have also identified the potential TNF-α inducing peptides in different proteins of HIV-1, HIV-2, SARS-CoV-2 and human insulin. Best models developed in this study has been incorporated in a webserver TNFepitope (https://webs.iiitd.edu.in/raghava/tnfepitope/), standalone package and GitLab (https://gitlab.com/raghavalab/tnfepitope).Key PointsTNF-α is a multifunctional pleiotropic pro-inflammatory cytokine.Anti-TNF-α therapy used as an effective treatment in several autoimmune disorders.Composition-based features generated using Pfeature for each peptide sequence.Alignment-based and alignment-free models developed.Prediction and scanning of TNF-α inducing regions in antigens.TNFepitope is available as a web-server, standalone package and GitLab.
Genetic basis ofArabidopsis thalianaresponses to infection by naïve and adapted isolates of turnip mosaic virus
Authors: Butković Anamarija , Ellis Thomas James , González Rubén , Jaegle Benjamin , Nordborg Magnus , Elena Santiago F. 
Published: August 2022

SummaryPlant viruses account for enormous agricultural losses worldwide, and the most effective way to combat them is to identify genetic material conferring plant resistance to these pathogens. Aiming to identify genetic associations with responses to infection, we screened a large panel ofArabidopsis thaliananatural inbred lines for four disease-related traits caused by infection byA. thaliana-naïve and -adapted isolates of the natural pathogen turnip mosaic virus (TuMV). We detected a strong, replicable association in a 1.5 Mb region on chromosome 2 with a 10-fold increase in relative risk of systemic necrosis. The region contains several plausible causal genes as well as abundant structural variation, including an insertion of aCopiatransposon into a Toll/interleukin receptor (TIR-NBS-LRR) coding for a gene involved in defense, that could be either a driver or a consequence of the disease-resistance locus. When inoculated with TuMV, loss-of-function mutant plants of this gene exhibited different symptoms than wild-type plants. The direction and severity of symptom differences depended on the adaptation history of the virus. This increase in symptoms severity was specific for infections with the adapted isolate. Necrosis-associated alleles are found worldwide, and their distribution is consistent with a trade-off between resistance during viral outbreaks and a cost of resistance otherwise, leading to negative frequency-dependent selection.
Human ATG3 contains a non-canonical LIR motif crucial for its enzymatic activity in autophagy
Authors: Farnung Jakob , Muhar Matthias , Liang Jin Rui , Tolmachova Kateryna A. , Benoit Roger M. , Corn Jacob E. , Bode Jeffrey W. 
Published: August 2022

AbstractMacroautophagy is one of two major degradation systems in eukaryotic cells. Regulation and control of autophagy is often achieved through the presence of short peptide sequences called LC3 interacting regions (LIR) in autophagy-involved proteins. Using a combination of new protein-derived activity-based probes, protein modelling and X-ray crystallography, we identified a non-canonical LIR motif in the human E2 enzyme responsible for LC3 lipidation, ATG3. The LIR motif is present in the flexible region of ATG3 and adopts an uncommon β-sheet structure binding to the backside of LC3. We show that the β-sheet conformation is crucial for its interaction with LC3. In cellulo studies provide evidence that LIRATG3 is required for LC3 lipidation and ATG3∼LC3 thioester formation. Removal of LIRATG3 negatively impacts the rate of thioester transfer from ATG7 to ATG3.Abstract Figure
Can pseudotopological models for SMC-driven DNA loop extrusion explain the traversal of physical roadblocks bigger than the SMC ring size?
Authors: Pradhan Biswajit , Barth Roman , Kim Eugene , Davidson Iain F. , van der Torre Jaco , Peters Jan-Michael , Dekker Cees 
Published: August 2022

SUMMARYDNA loop extrusion by structural-maintenance-of-chromosome (SMC) complexes has emerged as a primary organizing principle for chromosomes. The mechanism by which SMC motor proteins extrude DNA loops is still unresolved and much debated. The ring-like structure of SMC complexes prompted multiple models where the extruded DNA is topologically or pseudotopologically entrapped within the ring during loop extrusion. However, recent experiments showed the passage of roadblocks much bigger than the SMC ring size, suggesting a nontopological mechanism. Recently, attempts were made to reconcile the observed passage of large roadblocks with a pseudotopological mechanism. Here we examine the predictions of these pseudotopological models, and find that they are not consistent with some experimental data on SMC roadblock encounters. Particularly, these models predict the formation of two loops and that roadblocks will reside near the stem of the loop upon encounter – both in contrast to experimental observations. Overall, the experimental data reinforce the notion of a nontopological mechanism for extrusion of DNA.
Monkeypox Knowledge Graph: A comprehensive representation embedding chemical entities and associated biology of Monkeypox
Authors: Karki Reagon , Zaliani Andrea , Gadiya Yojana , Gribbon Philip 
Published: August 2022

AbstractSummaryThe outbreak of Monkeypox virus (MPXV) infection in May 2022 is declared a global health emergency by WHO. As of 28th July, 21067 cases have been confirmed and the numbers are on the rise. Unfortunately, MPXV pathophysiology and its underlying mechanisms are not yet understood. Likewise, the knowledge of biochemicals and drugs used against MPXV and their downstream effects is sparse. In this work, using Knowledge Graph (KG) representations we have depicted chemical and biological aspects of MPXV. To achieve this, we have collected and rationally assembled several biological study results, assays, drug candidates, and preclinical evidence to form a dynamic and comprehensive network. The KG is compliant with FAIR annotations allowing seamless transformation and integration to/with other formats and infrastructures.Availability and implementationThe Monkeypox knowledge graph is publicly available at https://github.com/Fraunhofer-ITMP/mpox-kgSupplementary informationSupplementary data are available at Bioinformatics online.ContactReagon.Karki@itmp.fraunhofer.de
Monkeypox DNA correlates with virus infectivity in clinical samples
Authors: Paran Nir , Yahalom-Ronen Yfat , Shifman Ohad , Lazar Shirley , Ben-Ami Ronen , Yakubovsky Michal , Levy Itzchak , Feinsod Anat Wieder , Amit Sharon , Katzir Michal , Oren Noga Carmi , Levcovich Ariela , Hershman-Sarafov Mirit , Paz Alona , Thomas Rebecca , Tamir Hadas , Cherry-Mimran Lilach , Erez Noam , Melamed Sharon , Barlev-Gross Moria , Karmi Shay , Politi Boaz , Achdout Hagit , Weiss Shay , Levy Haim , Schuster Ofir , Beth-Din Adi , Israely Tomer 
Published: August 2022

AbstractIn light of the alarming global spread of Monkeypox and the lack of data regarding virus infectivity in clinical specimens, we examined virus infectivity and its correlation with PCR results, the currently available diagnostic tool. Due to the high risk of Monkeypox virus infection, only a limited number of approved BSL-3 laboratories employed with vaccinated staff, including ourselves, are capable of determining Monkeypox virus infectivity. We show strong correlation between viral DNA content and virus infectivity in clinical specimens. Moreover, we define a PCR threshold value which correspond to non-infectious virus, and suggest that our data can be translated into informed decision-making regarding risk assessment, protective measures and guidelines for Monkeypox patients.
Cerebral blood volume sensitive layer-fMRI in the human auditory cortex at 7 Tesla: Challenges and capabilities
Authors: Faes Lonike K. , De Martino Federico , Huber Laurentius (Renzo) 
Published: August 2022

AbstractThe development of ultra high field (UHF) fMRI signal readout strategies and contrasts has led to the possibility of imaging the human brain in vivo and non-invasively at increasingly higher spatial resolutions of cortical layers and columns. One emergent layer-fMRI acquisition method with increasing popularity is the cerebral blood volume (CBV) sensitive sequence named vascular space occupancy (VASO). This approach has been shown to be mostly sensitive to locally-specific changes of laminar microvasculature, without unwanted biases of trans-laminar draining veins. Until now, however, VASO has not been applied in the technically challenging cortical area of the primary auditory cortex. Here, we developed a VASO imaging protocol for auditory neuroscientific applications. We describe the main challenges we encountered and the solutions we have adopted to mitigate them. With our optimized protocol, we investigate laminar responses to sounds. Finally, as proof of concept for future investigations, we map the topographic representation of frequency preference (tonotopy) in the auditory cortex.HighlightsLayer fMRI VASO in the auditory cortex is challenging due to its physiologyAfter protocol optimization we show the applicability of VASO to the auditory cortexTopographic maps obtained with VASO respect the large-scale tonotopic organization that has previously been shown with BOLD fMRI data.
Glabridin induces paraptosis-like cell death via ER stress in breast cancer cells
Authors: Cui Xiang , Cui Min 
Published: August 2022

AbstractGlabridin, a polyphenolic flavonoid isolated from the root of the glycyrrhiza glabra, has been demonstrated to have anti-tumor properties in human malignancies. This study found that glabridin decreased the viability of human breast cancer MDA-MB-231 and MCF7 cells in a dose-dependent manner that was not involved in the caspase-3 cascade. Glabridin promoted the formation of extensive cytoplasmic vacuolation by increasing the expression of endoplasmic reticulum (ER) stress markers BiP, XBP1s, and CHOP. The transmission electron microscopy and fluorescence with the ER chaperon KDEL suggested that the vacuoles were derived from ER. Glabridin-induced vacuolation was blocked when protein synthesis was inhibited by cycloheximide, demonstrating that protein synthesis is crucial for this process. Furthermore, we determined that glabridin causes loss of mitochondrial membrane potential as well as the production of reactive oxygen species, both of which lead to mitochondrial dysfunction. These features are consistent with a kind of programmed cell death described as paraptosis. This work reports for the first time that glabridin could induce paraptosis-like cell death, which may give new therapeutic approaches for apoptosis-resistant breast cancers.
An Algorithm for Sequence Location Approximation using Nuclear Families (ASLAN) Validates Regions of the Telomere-to-Telomere Assembly and Identifies New Hotspots for Genetic Diversity
Authors: Chrisman Brianna , He Chloe , Jung Jae-Yoon , Stockham Nate , Paskov Kelley , Washington Peter , Wall Dennis P. 
Published: August 2022

1AbstractAlthough it is heavily relied on to study genetic contributors to health and disease, the current human reference genome (GRCh38) is incomplete in two major ways: firstly, it is missing large sections of heterochromatic sequence, and secondly, as a singular, linear reference genome it does not represent the full spectrum of genetic diversity that exists in the human species. In order to better understand and characterize gaps in GRCh38 and genetic diversity, we developed a method - ASLAN, an Algorithm for Sequence Location Approximation using Nuclear families - that identifies the region of origin of short reads that do not align to the GRCh38. Using unmapped reads and variant calls from whole genome sequencing (WGS) data from nuclear families, ASLAN relies on a maximum likelihood model to identify the most likely region of the genome that a subsequence belongs to, given the phasing information of family and the distribution of the subsequence in the unmapped reads. Validating ASLAN on a synthetically generated dataset, and on true reads originating from the alternative haplotypes in the decoy genome, we show that ASLAN can localize more than 90% of 100-basepair sequences with above 92% accuracy and around 1 megabase of resolution. We then run ASLAN on 100-mers from unmapped reads from WGS from over 700 families, and compare ASLAN localizations to alignment of the 100-mers to the T2T-CHM13 assembly, recently released by the Telomere-to-telomere (T2T) consortia. We find that many unmapped reads in GRCh38 originate from telomeres and centromeres that are gaps in the GRCh38 reference. We also confirm that ASLAN localizations are in high concordance with T2T-CHM13 alignments, except in the centromeres of the acrocentric chromosomes. Comparing ASLAN localizations and T2T-CHM13 alignments, we identify sequences missing from T2T-CHM13 or sequences with high divergence from their aligned region in T2T-CHM13, thus highlighting new hotspots for genetic diversity.
Pattern formation and bistability in a synthetic intercellular genetic toggle
Authors: de Freitas Magalhães Bárbara , Fan Gaoyang , Sontag Eduardo , Josić Krešimir , Bennett Matthew R. 
Published: August 2022

SummaryDifferentiation within multicellular organisms is a complex process that helps to establish spatial patterning and tissue formation within the body. Often, the differentiation of cells is governed by morphogens and intercellular signaling molecules that guide the fate of each cell, frequently using toggle-like regulatory components. Synthetic biologists have long sought to recapitulate patterned differentiation with engineered cellular communities and various methods for differentiating bacteria have been invented. Here, we couple a synthetic co-repressive toggle switch with intercellular signaling pathways to create a “quorum-sensing toggle.” We show that this circuit not only exhibits population-wide bistability in a well-mixed liquid environment, but also generates patterns of differentiation in colonies grown on agar containing an externally supplied morphogen. If coupled to other metabolic processes, circuits such as the one described here would allow for the engineering of spatially patterned, differentiated bacteria for use in biomaterials and bioelectronics.