bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Antarctic Seafloor Annotated Imagery Database
Authors: Jansen Jan , Shelamoff Victor , Gros Charley , Windsor Thomas , Hill Nicole A. , Barnes David K. , Bowden David A. , Gutt Julian , Bax Narissa , Downey Rachel , Eléaume Marc , Post Alexandra L. , Griffiths Huw , Linse Katrin , Piepenburg Dieter , Purser Autun , Smith Craig R. , Ziegler Amanda F. , Johnson Craig R. 
Published: February 2023

AbstractMarine imagery is a comparatively cost-effective way to collect data on seafloor organisms, biodiversity and habitat morphology. However, annotating these images to extract detailed biological information is time-consuming and expensive, and reference libraries of consistently annotated seafloor images are rarely publicly available. Here, we present the Antarctic Seafloor Annotated Imagery Database (AS-AID), a result of a multinational collaboration to collate and annotate regional seafloor imagery datasets from 19 Antarctic research cruises between 1985 and 2019. AS-AID comprises of 3,599 georeferenced downward facing seafloor images that have been labelled with a total of 615,051 expert annotations. Annotations are based on the CATAMI (Collaborative and Automated Tools for Analysis of Marine Imagery) classification scheme and have been reviewed by experts. In addition, because the pixel location of each annotation within each image is available, annotations can be viewed easily and customised to suit individual research priorities.This dataset can be used to investigate species distributions, community patterns, it provides a reference to assess change through time, and can be used to train algorithms to automatically detect and annotate marine fauna.
Genome wide variation in the Angolan Namib desert reveals unique Pre-Bantu ancestry
Authors: Oliveira Sandra , Fehn Anne-Maria , Amorim Beatriz , Stoneking Mark , Rocha Jorge 
Published: February 2023

AbstractThe populations of the Angolan Namib Desert have been largely neglected in previous surveys of the genomic landscape of southern Africa. Although at present the Namib is culturally dominated by Southwest Bantu-speaking cattle-herders, the region exhibits an extraordinary ethnographic diversity which includes an array of semi-nomadic peoples whose subsistence strategies fall outside the traditional division between foraging and food production and can thus be referred to as “peripatetic”. Among these small-scale populations are the last speakers of the Kwadi branch of the Khoe-Kwadi language family associated with the introduction of pastoralism into southern Africa (Kwepe), as well as a range of groups whose origins remain enigmatic (Kwisi, Twa and Tjimba). Using genome-wide data from 208 individuals belonging to nine ethnically diverse groups from the Angolan Namib and adjacent areas (Kwepe, Kwisi, Twa, Tjimba, !Xun, Kuvale, Himba, Nyaneka, Ovimbundu) in combination with published data from other regions of Africa, we reconstruct in detail the histories of contact emerging from pre-historic migrations to southern Africa and show that peripatetic groups from southwestern Angola stand out for exhibiting elevated levels of an unique, regionally-specific and highly divergent Pre-Bantu ancestry. These findings highlight the importance of the Namib for understanding the deep genetic structure of Africa.
Transcriptional heterogeneity in human diabetic foot wounds
Authors: Sandoval-Schaefer Teresa , Phan Quan , Dash Biraja C. , Prassinos Alexandre J. , Duan Kaiti , Gazes Michael I. , Vyce Steven D. , Driskell Ryan , Hsia Henry C. , Horsley Valerie 
Published: February 2023

AbstractWound repair requires the coordination of multiple cell types including immune cells and tissue resident cells to coordinate healing and return of tissue function. Diabetic foot ulceration is a type of chronic wound that impacts over 4 million patients in the US and over 7 million worldwide (Edmonds et al., 2021). Yet, the cellular and molecular mechanisms that go awry in these wounds are not fully understood. Here, by profiling chronic foot ulcers from non-diabetic (NDFUs) and diabetic (DFUs) patients using single-cell RNA sequencing, we find that DFUs display transcription changes that implicate reduced keratinocyte differentiation, altered fibroblast function and lineages, and defects in macrophage metabolism, inflammation, and ECM production compared to NDFUs. Furthermore, analysis of cellular interactions reveals major alterations in several signaling pathways that are altered in DFUs. These data provide a view of the mechanisms by which diabetes alters healing of foot ulcers and may provide therapeutic avenues for DFU treatments.
Genetic Screen Uncovers a Dual Role for Phospholipids in Mitochondrial-Derived Compartment Biogenesis
Authors: Xiao Tianyao , English Alyssa M. , Maschek J. Alan , Cox James E. , Hughes Adam L. 
Published: February 2023

ABSTRACTCells utilize multiple mechanisms to maintain mitochondrial homeostasis in response to stress. We recently identified a cellular structure, called the mitochondria-derived compartment (MDC), that is generated from mitochondria in response to amino acid overabundance. MDCs selectively sequester proteins from mitochondria for subsequent degradation, and loss of MDCs sensitizes cells to amino acid stress. Here, we conducted a microscopy-based screen in budding yeast to identify factors that regulate MDC formation. We found that levels of two mitochondrial phospholipids, cardiolipin (CL) and phosphatidylethanolamine (PE), regulate MDC biogenesis in opposing directions. CL depletion impairs MDC biogenesis, whereas PE reduction leads to constitutive MDC formation. Additionally, in response to MDC-inducing agents, cellular and mitochondrial PE declines in an amino acid-dependent manner. Overexpressing mitochondrial PE synthesis pathway components suppresses MDC biogenesis during amino acid stress. Altogether, our data indicate a requirement for CL in MDC biogenesis, and suggest that PE depletion may serve as a regulatory signal for MDC formation downstream of MDC-inducing metabolic stress.SUMMARYXiao et al. identify distinct roles for the phospholipids cardiolipin and phosphatidylethanolamine in mitochondria-derived compartment (MDC) biogenesis. They show that cardiolipin is required for MDC formation, whereas a decline in phosphatidylethanolamine in response to amino acid stress triggers MDC biogenesis.
Mutual information networks reveal evolutionary relationships within the influenza A virus polymerase
Authors: Arcos Sarah , Han Alvin X. , te Velthuis Aartjan J. W. , Russell Colin A. , Lauring Adam S. 
Published: February 2023

AbstractThe influenza A (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits of the IAV polymerase (PB2, PB1, and PA). Evolutionary analysis of the IAV polymerase is complicated, because changes in mutation rate, replication speed, and drug resistance involve epistatic interactions among its subunits. In order to study the evolution of the human seasonal H3N2 polymerase since the 1968 pandemic, we identified pairwise evolutionary relationships among ∼7000 H3N2 polymerase sequences using mutual information (MI), which measures the information gained about the identity of one residue when a second residue is known. To account for uneven sampling of viral sequences over time, we developed a weighted MI metric (wMI) and demonstrate that wMI outperforms raw MI through simulations using a well-sampled SARS-CoV-2 dataset. We then constructed wMI networks of the H3N2 polymerase to extend the inherently pairwise wMI statistic to encompass relationships among larger groups of residues. We included HA in the wMI network to distinguish between functional wMI relationships within the polymerase and those potentially due to hitchhiking on antigenic changes in HA. The wMI networks reveal coevolutionary relationships among residues with roles in replication and encapsidation. Inclusion of HA highlighted polymerase-only subgraphs containing residues with roles in the enzymatic functions of the polymerase and host adaptability. This work provides insight into the factors that drive and constrain the rapid evolution of influenza viruses.
SOURSOP: A Python package for the analysis of simulations of intrinsically disordered proteins
Authors: Lalmansingh Jared M. , Keeley Alex T. , Ruff Kiersten M. , Pappu Rohit V. , Holehouse Alex S. 
Published: February 2023

ABSTRACTConformational heterogeneity is a defining hallmark of intrinsically disordered proteins and protein regions (IDRs). The functions of IDRs and the emergent cellular phenotypes they control are associated with sequence-specific conformational ensembles. Simulations of conformational ensembles that are based on atomistic and coarse-grained models are routinely used to uncover the sequence-specific interactions that may contribute to IDR functions. These simulations are performed either independently or in conjunction with data from experiments. Functionally relevant features of IDRs can span a range of length scales. Extracting these features requires analysis routines that quantify a range of properties. Here, we describe a new analysis suite SOURSOP, an object-oriented and open-source toolkit designed for the analysis of simulated conformational ensembles of IDRs. SOURSOP implements several analysis routines motivated by principles in polymer physics, offering a unique collection of simple-to-use functions to characterize IDR ensembles. As an extendable framework, SOURSOP supports the development and implementation of new analysis routines that can be easily packaged and shared.
FriendlyClearMap: An optimized toolkit for mouse brain mapping and analysis
Authors: Negwer Moritz , Bosch Bram , Bormann Maren , Hesen Rick , Lütje Lukas , Aarts Lynn , Rossing Carleen , Kasri Nael Nadif , Schubert Dirk 
Published: February 2023

AbstractTissue clearing is currently revolutionizing neuroanatomy by enabling organ-level imaging with cellular resolution. However, currently available tools for data analysis require a significant time investment for training and adaptation to each laboratory’s use case, which limits productivity. Here, we present FriendlyClearMap, an integrated toolset that makes ClearMap1 and ClearMap2’s CellMap pipeline easier to use, extends its functions, and provides Docker Images from which it can be run with minimal time investment. We also provide detailed tutorials for each step of the pipeline.For more precise alignment, we add a landmark-based atlas registration to ClearMap’s functions as well as include young mouse reference atlases for developmental studies. We provide alternative cell segmentation method besides ClearMap’s threshold-based approach: Ilastik’s Pixel Classification, importing segmentations from commercial image analysis packages and even manual annotations. Finally, we integrate BrainRender, a recently released visualization tool for advanced 3D visualization of the annotated cells.As a proof-of-principle, we use FriendlyClearMap to quantify the distribution of the three main GABAergic interneuron subclasses (Parvalbumin+, Somatostatin+, and VIP+) in the mouse fore- and midbrain. For PV+neurons, we provide an additional dataset with adolescent vs. adult PV+neuron density, showcasing the use for developmental studies. When combined with the analysis pipeline outlined above, our toolkit improves on the state-of-the-art packages by extending their function and making them easier to deploy at scale.
The Essential Role of O-GlcNAcylation in Hepatic Differentiation
Authors: Robarts Dakota R. , Kotulkar Manasi , Paine-Cabrera Diego , Venneman Kaitlyn K. , Hanover John A. , Zachara Natasha E. , Slawson Chad , Apte Udayan 
Published: February 2023

AbstractBackground & AimsO-GlcNAcylation is a post-translational modification catalyzed by the enzyme O-GlcNAc transferase (OGT), which transfers a single N-acetylglucosamine sugar from UDP-GlcNAc to the protein on serine and threonine residues on proteins. Another enzyme, O-GlcNAcase (OGA), removes this modification. O-GlcNAcylation plays an important role in pathophysiology. Here, we report that O-GlcNAcylation is essential for hepatocyte differentiation, and chronic loss results in fibrosis and hepatocellular carcinoma.MethodsSingle-cell RNA-sequencing was used to investigate hepatocyte differentiation in hepatocyte-specific OGT-KO mice with increased hepatic O-GlcNAcylation and in OGA-KO mice with decreased O-GlcNAcylation in hepatocytes. HCC patient samples and the DEN-induced hepatocellular carcinoma (HCC) model were used to investigate the effect of modulation of O-GlcNAcylation on the development of liver cancer.ResultsLoss of hepatic O-GlcNAcylation resulted in disruption of liver zonation. Periportal hepatocytes were the most affected by loss of differentiation characterized by dysregulation of glycogen storage and glucose production. OGT-KO mice exacerbated DEN-induced HCC development with increased inflammation, fibrosis, and YAP signaling. Consistently, OGA-KO mice with increased hepatic O-GlcNAcylation inhibited DEN-induced HCC. A progressive loss of O-GlcNAcylation was observed in HCC patients.ConclusionsOur study shows that O-GlcNAcylation is a critical regulator of hepatic differentiation, and loss of O-GlcNAcylation promotes hepatocarcinogenesis. These data highlight increasing O-GlcNAcylation as a potential therapy in chronic liver diseases, including HCC.Lay SummaryProteins in cells are modified by the addition of a single glucosamine sugar molecule called O-GlcNAcylation. Loss of O-GlcNAcylation in hepatocytes, the most common type of cells in the liver, causes the liver to lose its function and can result in increased liver diseases such as fibrosis and cancer.Graphical AbstractHighlightsSingle-Cell RNA-sequencing reveals loss of metabolic liver zonation in O-GlcNAcylation deficient livers.Loss of O-GlcNAcylation promoted DEN-Induced HCC.Increase of hepatic O-GlcNAcylation prevented HCC progression.
Crosstalk in skin: Loss of desmoglein 1 in keratinocytes inhibits BRAFV600E-induced cellular senescence in human melanocytes
Authors: Tong Xin , Burks Hope E. , Ren Ziyou , Koetsier Jennifer L. , Roth-Carter Quinn R. , Green Kathleen J. 
Published: February 2023

AbstractMelanoma arises from transformation of melanocytes in the basal layer of the epidermis where they are surrounded by keratinocytes, with which they interact through cell contact and paracrine communication. Considerable effort has been devoted to determining how the accumulation of oncogene and tumor suppressor gene mutations in melanocytes drive melanoma development. However, the extent to which alterations in keratinocytes that occur in the developing tumor niche serve as extrinsic drivers of melanoma initiation and progression is poorly understood. We recently identified the keratinocyte-specific cadherin, desmoglein 1 (Dsg1), as an important mediator of keratinocyte:melanoma cell crosstalk, demonstrating that its chronic loss, which can occur through melanoma cell-dependent paracrine signaling, promotes behaviors that mimic a malignant phenotype. Here we address the extent to which Dsg1 loss affects early steps in melanomagenesis. RNA-Seq analysis revealed that paracrine signals from Dsg1-deficient keratinocytes mediate a transcriptional switch from a differentiated to undifferentiated cell state in melanocytes expressing BRAFV600E, a driver mutation commonly present in both melanoma and benign nevi and reported to cause growth arrest and oncogene-induced senescence (OIS). Of ∼220 differentially expressed genes in BRAFV600Ecells treated with Dsg1-deficient conditioned media (CM), the laminin superfamily member NTN4/Netrin-4, which inhibits senescence in endothelial cells, stood out. Indeed, while BRAFV600Emelanocytes treated with Dsg1-deficient CM showed signs of senescence bypass as assessed by increased senescence-associated β-galactosidase activity and decreased p16, knockdown of NTN4 reversed these effects. These results suggest that Dsg1 loss in keratinocytes provides an extrinsic signal to push melanocytes towards oncogenic transformation once an initial mutation has been introduced.
Bacterial multispecies invasion of human epithelial bladder cells
Authors: Abell-King Charlotte , Pokhrel Alaska , Rice Scott A. , Duggin Iain G. , Söderström Bill 
Published: February 2023

AbstractUrinary tract infections (UTI) are one of the most common bacterial infections worldwide. While the overall infection course is known on a macroscale, bacterial behavior is not fully understood at the cellular level and bacterial pathophysiology during multispecies infection is not well characterized. Here we establish co-infection models combined with high resolution imaging to compare single- and multi-species bladder cell invasion events in three common uropathogens: uropathogenicEscherichia coli(UPEC),Klebsiella pneumoniaeandEnterococcus faecalis. While all three species invaded the bladder cells, under flow conditions the Gram-positiveE. faecaliswas significantly less invasive compared to the Gram-negative UPEC andK. pneumoniae. When introduced simultaneously during an infection experiment, all three bacterial species sometimes invaded the same bladder cell, at differing frequencies suggesting complex interactions between bacterial species and bladder cells. Inside host cells, we observed encasement ofE. faecaliscolonies specifically by UPEC. During subsequent dispersal from the host cells, only the Gram-negative bacteria underwent infection-related filamentation (IRF). Taken together, our data suggest that bacterial multispecies invasions of single bladder cells are frequent and support earlier studies showing intraspecies cooperation on a biochemical level during UTI.
Proximity-dependent biotinylation and identification of flagellar proteins inTrypanosoma cruzi
Authors: Won Madalyn M. , Baublis Aaron , Burleigh Barbara A. 
Published: February 2023

AbstractThe flagellated kinetoplastid protozoan and causative agent of human Chagas disease,Trypanosoma cruzi, inhabits both invertebrate and mammalian hosts over the course of its complex life cycle. In these disparate environments,T. cruziuses its single flagellum to propel motile life stages and in some instances, to establish intimate contact with the host. Beyond its role in motility, the functional capabilities of theT. cruziflagellum have not been defined. Moreover, the lack of proteomic information for this organelle, in any parasite life stage, has limited functional investigation. In this study, we employed a proximity-dependent biotinylation approach based on the differential targeting of the biotin ligase, TurboID, to the flagellum or cytosol in replicative stages ofT. cruzi, to identify flagellar-enriched proteins by mass spectrometry. Proteomic analysis of the resulting biotinylated protein fractions yielded 218 candidate flagellar proteins inT. cruziepimastigotes (insect stage) and 99 proteins in intracellular amastigotes (mammalian stage). Forty of these flagellar-enriched proteins were common to both parasite life stages and included orthologs of known flagellar proteins in other trypanosomatid species, proteins specific to theT. cruzilineage and hypothetical proteins. With the validation of flagellar localization for several of the identified candidates, our results demonstrate that TurboID-based proximity proteomics is an effective tool for probing subcellular compartments inT. cruzi.The proteomic datasets generated in this work offer a valuable resource to facilitate functional investigation of the understudiedT. cruziflagellum.ImportanceTrypanosoma cruziis a protozoan parasite that causes Chagas disease, which contributes substantial morbidity and mortality in South and Central America. Throughout its life cycle,T. cruziinteracts with insect and mammalian hosts via its single flagellum, establishing intimate contact with host membranes. Currently, few flagellar proteins have been identified inT. cruzithat could provide insight into the mechanisms involved in mediating physical and biochemical interactions with the host. Here, we set out to identify flagellar proteins in the main replicative stages ofT. cruziusing a proximity-labeling approach coupled with mass spectrometry. The >200 candidate flagellar proteins identified represent the first large scale identification of candidate flagellar proteins inT. cruziwith preliminary validation. These data offer new avenues to investigate the biology ofT. cruzi- host interactions, a promising area for development of new strategies aimed at the control of this pathogen.
Broad sensitivity ofCandida aurisstrains to quinolones and mechanisms of resistance
Authors: Lohse Matthew B. , Laurie Matthew T. , Levan Sophia , Ziv Naomi , Ennis Craig L. , Nobile Clarissa J. , DeRisi Joseph , Johnson Alexander D. 
Published: February 2023

AbstractThe fungal pathogenCandida aurisrepresents a severe threat to hospitalized patients. Its resistance to multiple classes of antifungal drugs and ability to spread and resist decontamination in health-care settings make it especially dangerous. We screened 1,990 clinically approved and late-stage investigational compounds for the potential to be repurposed as antifungal drugs targetingC. aurisand narrowed our focus to five FDA-approved compounds with inhibitory concentrations under 10 µM forC. aurisand significantly lower toxicity to three human cell lines. These compounds, some of which had been previously identified in independent screens, include three dihalogenated 8-hydroxyquinolines: broxyquinoline, chloroxine, and clioquinol. A subsequent structure-activity study of 32 quinoline derivatives found that 8-hydroxyquinolines, especially those dihalogenated at the C5 and C7 positions, were the most effective inhibitors ofC. auris. To pursue these compounds further, we exposedC. auristo clioquinol in an extended experimental evolution study and found thatC. aurisdeveloped only 2- to 5-fold resistance to the compound. DNA sequencing of resistant strains and subsequent verification by directed mutation in naive strains revealed that resistance was due to mutations in the transcriptional regulatorCAP1(causing upregulation of the drug transporterMDR1) and in the drug transporterCDR1. These mutations had only modest effects on resistance to traditional antifungal agents, and theCDR1mutation renderedC. aurismore sensitive to posaconazole. This observation raises the possibility that a combination treatment involving an 8-hydroxyquinoline and posaconazole might preventC. aurisfrom developing resistance to this established antifungal agent.Abstract ImportanceThe rapidly emerging fungal pathogenCandida aurisrepresents a growing threat to hospitalized patients, in part due to frequent resistance to multiple classes of antifungal drugs. We identify a class of compounds, the dihalogenated hydroxyquinolines, with broad fungistatic ability against a diverse collection of 13 strains ofC. auris. Although this compound has been identified in previous screens, we extended the analysis by showing thatC. aurisdeveloped only modest 2- to 5-fold increases in resistance to this class of compounds despite long-term exposure; a noticeable difference from the 30- to 500- fold increases in resistance reported for similar studies with commonly used antifungal drugs. We also identify the mutations underlying the resistance. These results suggest that the dihalogenated hydroxyquinolines are working inside the fungal cell and should be developed further to combatC. aurisand other fungal pathogens.TweetLohse and colleagues characterize a class of compounds that inhibit the fungal pathogenC. auris. Unlike many other antifungal drugs,C. aurisdoes not readily develop resistance to this class of compounds.