bluuebunny/crossref_metadata_2025_split huggingface dataset:
Raman spectral analysis of microbial pigment compositions in vegetative cells and heterocysts of multicellular cyanobacterium
Authors: Ishihara Jun-ichi , Takahashi Hiroki 
Published: February 2023

AbstractThe one-dimensional multicellular cyanobacterium,Anabaenasp. PCC 7120, exhibits a simple topology consisting of two types of cells under the nitrogen-depleted conditions. Although the differentiated (heterocyst) and undifferentiated cells (vegetative cells) were distinguished by their cellular shapes, we found that their internal states, that is, microbial pigment compositions, were distinguished by using a Raman microscope. Almost of Raman bands of the cellular components were assigned to vibrations of the pigments; chlorophylla, β-carotene, phycocyanin, and allophycocyanin. We found that the Raman spectral measurement can detect the decomposition of both phycocyanin and allophycocyanin, which are components of the light-harvesting phycobilisome complex in the photosystem II. We observed that the Raman bands of phycocyanin and allophycocyanin exhibited more remarkable decrease in the heterocysts when compared to those of chlorophyllaand β-carotene. This result indicated the prior decomposition of phycobilisome in the heterocysts. Moreover, the Raman bands of allophycocyanin were more decreased in heterocysts when compared to those of phycocyanin, suggesting that the decomposition of phycocyanin was more strongly suppressed than allophycocyanin in heterocysts. We show that the Raman measurement is useful to detect the change of pigment composition in the cell differentiation.
The HRA Organ Gallery Affords Immersive Superpowers for Building and Exploring the Human Reference Atlas with Virtual Reality
Authors: Bueckle Andreas , Qing Catherine , Luley Shefali , Kumar Yash , Pandey Naval , Börner Katy 
Published: February 2023

AbstractThe Human Reference Atlas (HRA,https://humanatlas.io) funded by the NIH Human Biomolecular Atlas Program (HuBMAP,https://commonfund.nih.gov/hubmap) and other projects engages 17 international consortia to create a spatial reference of the healthy adult human body at single-cell resolution. The specimen, biological structure, and spatial data that define the HRA are disparate in nature and benefit from a visually explicit method of data integration. Virtual reality (VR) offers unique means to enable users to explore complex data structures in a threedimensional (3D) immersive environment. On a 2D desktop application, the 3D spatiality and real-world size of the 3D reference organs of the atlas is hard to understand. If viewed in VR, the spatiality of the organs and tissue blocks mapped to the HRA can be explored in their true size and in a way that goes beyond traditional 2D user interfaces. Added 2D and 3D visualizations can then provide data-rich context. In this paper, we present the HRA Organ Gallery, a VR application to explore the atlas in an integrated VR environment. Presently, the HRA Organ Gallery features 55 3D reference organs,1,203 mapped tissue blocks from 292 demographically diverse donors and 15 providers that link to 5,000+ datasets; it also features prototype visualizations of cell type distributions and 3D protein structures. We outline our plans to support two biological use cases:on-ramping novice and expert users to HuBMAP data available via the Data Portal(https://portal.hubmapconsortium.org), andquality assurance/quality control (QA/QC) for HRA data providers. Code and onboarding materials are available athttps://github.com/cns-iu/ccf-organ-vr-gallery#readme.
P-Selectin promotes SARS-CoV-2 interactions with platelets and the endothelium
Authors: Moreno Cesar L. , Castanheira Fernanda V. S. , Stella Alberto Ospina , Chung Felicity , Aggarwal Anupriya , Cole Alexander J. , Loo Lipin , Dupuy Alexander , Kong Yvonne , Hagimola Lejla , Fenwick Jemma , Coleman Paul , Willson Michelle , Bui-Marinos Maxwell , Hesselson Daniel , Gamble Jennifer , Passam Freda , Turville Stuart , Kubes Paul , Neely G. Gregory 
Published: February 2023

AbstractCOVID-19 causes a clinical spectrum of acute and chronic illness and host / virus interactions are not completely understood1,2. To identify host factors that can influence SARS-CoV-2 infection, we screened the human genome for genes that, when upregulated, alter the outcome of authentic SARS-CoV-2 infection. From this, we identify 34 new genes that can alter the course of infection, including the innate immune receptor P-selectin, which we show is a novel SARS-CoV-2 spike receptor. At the cellular level expression of P-selectin does not confer tropism for SARS-CoV-2, instead it acts to suppress infection. More broadly, P-selectin can also promote binding to SARS-CoV-2 variants, SARS-CoV-1 and MERS, acting as a general spike receptor for highly pathogenic coronaviruses. P-selectin is expressed on platelets and endothelium3, and we confirm SARS-CoV-2 spike interactions with these cells are P-selectin-dependent and can occur under shear flow conditions.In vivo, authentic SARS-CoV-2 uses P-selectin to home to airway capillary beds where the virus interacts with the endothelium and platelets, and blocking this interaction can clear vascular-associated SARS-CoV-2 from the lung. Together we show for the first time that coronaviruses can use the leukocyte recruitment system to control tissue localization, and this fundamental insight may help us understand and control highly pathogenic coronavirus disease progression.
Optimal evaluation of energy yield and driving force in microbial metabolic pathway variants
Authors: Taha Ahmed , Penas David R , Patón Mauricio , Banga Julio R , Rodríguez Jorge 
Published: February 2023

AbstractThis work presents a methodology to evaluate the bioenergetic feasibility of alternative metabolic pathways for a given microbial conversion, optimising their energy yield and driving forces as a function of the concentration of metabolic intermediates. The tool, based on thermodynamic principles and multi-objective optimisation, accounts for pathway variants in terms of different electron carriers, as well as energy conservation (proton translocating) reactions within the pathway. The method also accommodates other constraints, some of them non-linear, such as the balance of conserved moieties. The approach involves the transformation of the maximum energy yield problem into a multi-objective linear optimisation problem which is then subsequently solved using the epsilon-constraint method, highlighting the trade-off between yield and rate in metabolic reactions. The methodology is applied to analyse several pathway alternatives occurring during propionate oxidation in anaerobic fermentation processes, as well as to the reverse TCA cycle pathway occurring during autotrophic microbial CO2fixation. The results obtained using the developed methodology match previously reported literature, and bring about insights into the studied pathways.
Quantitative classification of energy landscapes inferred from single nanoparticle tracking of membrane receptors inside nanodomains reveals confinement functional and molecular features
Authors: Yu Chao , Richly Maximilian , Hoang Thi Thuy , El Beheiry Mohammed , Türkcan Silvan , Masson Jean-Baptiste , Alexandrou Antigoni , Bouzigues Cedric I. 
Published: February 2023

ABSTRACTThe cell membrane organization has been hypothesized for a long time to have an essential functional role, through the control of membrane receptor confinement in micro- or nanodomains. Several mechanisms have been proposed to account for these properties, though some features of the resulting organization have remained controversial, notably the nature, size, and stability of cholesterol- and sphingolipid-rich domains called rafts.Here, we quantitatively probed the energy landscape experienced by single nanoparticle-labeled membrane receptors - epidermal growth factor receptors (EGFR), transferrin receptors (TfR), and receptors of ε-toxin produced byC. perfringensand α-toxin ofC.Septicum(CPεTR and CSαTR, respectively) - through the development of new computational methods. By establishing a new analysis pipeline combining Bayesian inference, decision trees and clustering approaches, we indeed systematically classified single protein trajectories according to the type of confining energy landscape. This revealed the existence of only two distinct organization modalities: (A) confinement in a quadratic energy landscape for EGF, CPεT and CSαT receptors and (B) free diffusion in confinement domains resulting from the steric hindrance due to F-actin barriers for transferrin receptors.The characterization of confinement energy landscapes by Bayesian inference furthermore revealed the role of interactions with the domain environment in cholesterol- and sphingolipid-rich domains with (in the case of EGFR) or without (for CPεT and CSαT receptors) parallel interactions with F-actin, to regulate the confinement energy depth. Strikingly, these two distinct mechanisms result in the same organization type (A). We furthermore revealed that the apparent domain sizes for these receptor trajectories resulted from Brownian exploration of the energy landscape in a steady-state like regime at a common effective temperature, independently of the underlying molecular mechanisms. These results highlight that the membrane organization in confinement domains may be more adequately described as interaction hotspots rather than rafts with abrupt domain boundaries.Altogether, these results establish a new computational approach, which paves the way to the constitution of an atlas of energy landscape of membrane proteins and of their control mechanisms, and support a new general model for functional receptor confinement in membrane nanodomains.
Modelling Phenomenological Differences in Aetiologically Distinct Visual Hallucinations Using Deep Neural Networks
Authors: Suzuki Keisuke , Seth Anil K. , Schwartzman David J. 
Published: February 2023

AbstractVisual hallucinations (VHs) are perceptions of objects or events in the absence of the sensory stimulation that would normally support such perceptions. Although all VHs share this core characteristic, there are substantial phenomenological differences between VHs that have different aetiologies, such as those arising from neurological conditions, visual loss, or psychedelic compounds. Here, we examine the potential mechanistic basis of these differences by leveraging recent advances in visualising the learned representations of a coupled classifier and generative deep neural network – an approach we call ‘computational (neuro)phenomenology’. Examining three aetiologically distinct populations in which VHs occur - neurological conditions (Parkinson’s Disease and Lewy Body Dementia), visual loss (Charles Bonnet Syndrome, CBS), and psychedelics - we identify three dimensions relevant to distinguishing these classes of VHs: realism (veridicality), dependence on sensory input (spontaneity), and complexity. By selectively tuning the parameters of the visualisation algorithm to reflect influence along each of these phenomenological dimensions we were able to generate ‘synthetic VHs’ that were characteristic of the VHs experienced by each aetiology. We verified the validity of this approach experimentally in two studies that examined the phenomenology of VHs in neurological and CBS patients, and in people with recent psychedelic experience. These studies confirmed the existence of phenomenological differences across these three dimensions between groups, and crucially, found that the appropriate synthetic VHs were representative of each group’s hallucinatory phenomenology. Together, our findings highlight the phenomenological diversity of VHs associated with distinct causal factors and demonstrate how a neural network model of visual phenomenology can successfully capture the distinctive visual characteristics of hallucinatory experience.
Orthogonal outlier detection and dimension estimation for improved MDS embedding of biological datasets
Authors: Li Wanxin , Mirone Jules , Prasad Ashok , Miolane Nina , Legrand Carine , Duc Khanh Dao 
Published: February 2023

AbstractConventional dimensionality reduction methods like Multidimensional Scaling (MDS) are sensitive to the presence of orthogonal outliers, leading to significant defects in the embedding. We introduce a robust MDS method, called DeCOr-MDS (Detection and Correction of Orthogonal outliers using MDS), based on the geometry and statistics of simplices formed by data points, that allows to detect orthogonal outliers and subsequently reduce dimensionality. We validate our methods using synthetic datasets, and further show how it can be applied to a variety of large real biological datasets, including cancer image cell data and human microbiome project data.
NeoTCR: an immunoinformatic database of experimentally-supported functional neoantigen-specific TCR sequences
Authors: Zhou Weijun , Xiang Wenting , Yu Jinyi , Ruan Zhihan , Pan Yichen , Wang Kankan , Liu Jian 
Published: February 2023

AbstractNeoantigen-based immunotherapy has demonstrated of long-lasting antitumor activity. Recognition of neoantigens by T cell receptors (TCRs) is considered a trigger for antitumor responses. Due to the overwhelming number of TCR repertoires in the human genome, it is challenging to computationally pinpoint neoantigen-specific TCRs. Recent studies have identified a number of functional neoantigen-specific TCRs, but the corresponding information is scattered across published literature and is difficult to retrieve. To improve access to these data, we developed the NeoTCR, an immunoinformatic database containing a unified description of publicly available neoantigen-specific TCR sequences, as well as relevant information on targeted neoantigens, from experimentally supported studies across 18 cancer subtypes. A user-friendly web interface allows interactive browsing and running of complex database queries based on numerous criteria. To facilitate rapid identification of neoantigen-specific TCRs from raw sequencing data, NeoTCR offers a one-stop analysis for annotation and visualization of TCR clonotypes, discovery of existing neoantigen-specific TCRs, and exclusion of bystander viral-associated TCRs. NeoTCR will serve as a valuable platform to study the biological functions of neoantigen-associated T-cells in anti-tumor immunity to better apply neoantigen-specific TCRs in clinics. NeoTCR is available athttp://www.neotcrdb.com/.
Mitochondrial Pyruvate Carrier Inhibition Attenuates Hepatic Stellate Cell Activation and Liver Injury in a Mouse Model of Metabolic Dysfunction-associated Steatotic Liver Disease
Authors: Habibi Mohammad , Ferguson Daniel , Eichler Sophie J. , Chan Mandy M. , LaPoint Andrew , Shew Trevor M. , He Mai , Lutkewitte Andrew J. , Schilling Joel D. , Cho Kevin Y. , Patti Gary J. , Finck Brian N. 
Published: February 2023

ABSTRACTHepatic stellate cells (HSC) are non-parenchymal liver cells that produce extracellular matrix comprising fibrotic lesions in chronic liver diseases. Prior work demonstrated that mitochondrial pyruvate carrier (MPC) inhibitors suppress HSC activation and fibrosis in a mouse model of metabolic dysfunction-associated steatohepatitis (MASH). In the present study, pharmacologic or genetic inhibition of the MPC in HSC decreased expression of markers of activationin vitro. MPC knockdown also reduced the abundance of several intermediates of the TCA cycle, and diminished α-ketoglutarate played a key role in attenuating HSC activation by suppressing hypoxia inducible factor-1α signaling. On high fat diets, mice with HSC-specific MPC deletion exhibited reduced circulating transaminases, numbers of HSC, and hepatic expression of markers of HSC activation and inflammation compared to wild-type mice. These data suggest that MPC inhibition modulates HSC metabolism to attenuate activation and illuminate mechanisms by which MPC inhibitors could prove therapeutically beneficial for treating MASH.
DeepTAP: an RNN-based method of TAP-binding peptide prediction in the selection of tumor neoantigens
Authors: Zhang Xue , Wu Jingcheng , Baeza Joseph , Gu Katie , Zhou Zhan 
Published: February 2023

AbstractThe transport of antigenic peptides from cytoplasm to the endoplasmic reticulum (ER) via transporter associated with antigen processing (TAP) is a critical step during the presentation of tumor neoantigens. The application of computational approaches significantly speed up the analysis of this biological process. Here, we present a tool named DeepTAP for TAP-binding peptide prediction, which employs a sequence-based multilayered recurrent neural network (RNN). Compared with traditional machine learning and other available prediction tools, DeepTAP achieves state-of-the-art performance on the benchmark datasets. The source code and dataset of DeepTAP are available freely via GitHub athttps://github.com/zjupgx/DeepTAP.
kakapo: Easy extraction and annotation of genes from raw RNA-seq reads
Authors: Ramanauskas Karolis , Igić Boris 
Published: February 2023

Abstractkakapo(kākāpō) is a python-based pipeline that allows users to extract and assemble one or more specified genes or gene families. It flexibly uses original RNA-seq read or GenBank SRA accession inputs without performing assembly of entire transcriptomes. The pipeline identifies open reading frames in the assembled gene transcripts and annotates them. It optionally filters raw reads for ribosomal, plastid, and mitochondrial reads, or reads belonging to non-target organisms (e.g., viral, bacterial, human).kakapocan be employed to extract arbitrary loci, such as those commonly used for phylogenetic inference in systematics or candidate genes and gene families in phylogenomic and metagenomic studies. We provide example applications and discuss how its use can offset the declining value of the GenBank’s single-gene databases and help assemble datasets for a variety of phylogenetic analyses.
Transmembrane protein CD69 acts as an S1PR1 agonist
Authors: Chen Hongwen , Qin Yu , Chou Marissa , Cyster Jason G. , Li Xiaochun 
Published: February 2023

AbstractThe activation of Sphingosine-1-phosphate receptor 1 (S1PR1) by S1P promotes lymphocyte egress from lymphoid organs, a process critical for immune surveillance and T cell effector activity1-4. Multiple drugs that inhibit S1PR1 function are in use clinically for the treatment of autoimmune diseases. Cluster of Differentiation 69 (CD69) is an endogenous negative regulator of lymphocyte egress that interacts with S1PR1 incisto facilitate internalization and degradation of the receptor5,6. The mechanism by which CD69 causes S1PR1 internalization has been unclear. Moreover, although there are numerous class A GPCR structures determined with different small molecule agonists bound, it remains unknown whether a transmembrane protein per se can act as a class A GPCR agonist. Here, we present the cryo-EM structure of CD69-bound S1PR1 coupled to the heterotrimeric Gicomplex. The transmembrane helix (TM) of one protomer of CD69 homodimer contacts the S1PR1-TM4. This interaction allosterically induces the movement of S1PR1-TMs 5-6, directly activating the receptor to engage the heterotrimeric Gi. Mutations in key residues at the interface affect the interactions between CD69 and S1PR1, as well as reduce the receptor internalization. Thus, our structural findings along with functional analyses demonstrate that CD69 acts incisas a protein agonist of S1PR1, thereby promoting Gi-dependent S1PR1 internalization, loss of S1P gradient sensing, and inhibition of lymphocyte egress.
The SapM phosphatase arrests phagosome maturation in an ESX-1 independent manner inMycobacterium tuberculosisand BCG
Authors: Xander Christian , Rajagopalan Saranathan , Jacobs William R , Braunstein Miriam 
Published: February 2023

AbstractMycobacterium tuberculosis(Mtb) is an intracellular pathogen that survives and grows in macrophages. A mechanism used byMtbto achieve intracellular survival is to secrete effector molecules that arrest the normal process of phagosome maturation. Through phagosome maturation arrest (PMA),Mtbremains in an early phagosome and avoids delivery to degradative phagolysosomes. One PMA effector ofMtbis the secreted SapM phosphatase. Because the host target of SapM, phosphatidylinositol-3-phosphate (PI3P), is located on the cytosolic face of the phagosome, SapM needs to be both released by the mycobacteria and escape the phagosome to carry out its function. To date, the only mechanism known forMtbmolecules to escape the phagosome is phagosome permeabilization by the ESX-1 secretion system. To understand this step of SapM function in PMA, we generated identical in-framesapMmutants in both the attenuatedMycobacterium bovisbacille Calmette-Guérin (BCG) vaccine strain, which lacks the ESX-1 system, andMtb. Characterization of these mutants demonstrated that SapM is required for PMA in both BCG andMtb. Further, by establishing a role for SapM in PMA in BCG, and subsequently in aMtbmutant lacking the ESX-1 system, we demonstrated that the role of SapM is ESX-1-independent. We further determined that ESX-2 or ESX-4 are also not required for SapM to function in PMA. These results indicate that SapM is a secreted effector of PMA in both BCG andMtband that it functions independent of the known mechanism forMtbmolecules to escape the phagosome.
Dysregulated miR-3959-3p in response to Lumpy skin disease virus
Authors: Pandita Sakshi , Singh Davinder , Kumar Naveen , Chander Yogesh 
Published: February 2023

AbstractLumpy skin disease virus (LSDV), a member of theCapripoxvirusgenus, causes substantial economic losses in the livestock industry and is rapidly spreading among various LSDV-free countries across the globe. Viral infections are known to alter the cellular miRNA expression profile of the host significantly.Besides being important biomarker candidates, circulating miRNAs have a significant role in controlling viral infection and antiviral immune responses, including several molecular mechanisms. miR-3959-3p, a significantly downregulated miRNA revealed in RNA-sequencing results of LSDV-infected LT cells, was selected to bedetected in the serum of LSDV-infected and uninfected cattle sera (40 LSDV-infected and 40 LSDV-uninfected). We optimized quantitative real-time PCR (qRT-PCR) for quantitative determination of miR-3959-3p in the bovine sera samples. The level of miR-3959-3p appears to be towards lower side in the LSDV-infected as compared to the uninfected animals. However, no significant correlation could be established between the two groups due to fluctuations in the miRNA levels in both groups. This is the first report on the detection of circulating miRNA in LSDV-infected cattle sera.The dysregulation pattern of miR-3959-3p appears to suggest that several other miRNAs need to be explored and may serve as biomarkers for LSDV infection. However, this needs further investigation by screening several other miRNAs and on large number of LSDV positive and negative animals.Author summaryMicroRNAs are the key regulators of viral infections. However, in LSDVinfection the miRNA response is greatly unknown.In this study, miRNA expression in Vero cell linepost LSDV infection was studied for the first time.One of the miRNAs identified in the RNA-sequencing results i.emiR-3959-3p, was shown to be downregulated LSDV infection. We detected the levels of mir-3959-3p in sera of LSDV-infected and uninfected cattle to explore its potential as a biomarker.