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  1. Article ; Online: Untangling Cellular Host-Pathogen Encounters at Infection Bottlenecks.

    Avraham, Roi

    Infection and immunity

    2023  Volume 91, Issue 4, Page(s) e0043822

    Abstract: Bacterial pathogens can invade the tissue and establish a protected intracellular niche at the site of invasion that can spread locally (e.g., microcolonies) or to systemic sites (e.g., granulomas). Invasion of the tissue and establishment of ... ...

    Abstract Bacterial pathogens can invade the tissue and establish a protected intracellular niche at the site of invasion that can spread locally (e.g., microcolonies) or to systemic sites (e.g., granulomas). Invasion of the tissue and establishment of intracellular infection are rare events that are difficult to study in the
    MeSH term(s) Salmonella ; Macrophages/microbiology ; Bacteria ; Host-Pathogen Interactions
    Language English
    Publishing date 2023-03-20
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/iai.00438-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Single-Molecule Fluorescent In Situ Hybridization (smFISH) for RNA Detection in Bacteria.

    Ciolli Mattioli, Camilla / Avraham, Roi

    Methods in molecular biology (Clifton, N.J.)

    2024  Volume 2784, Page(s) 3–23

    Abstract: In this chapter, we describe in detail how to perform a successful smFISH experiment and how to quantify mRNA transcripts in bacterial cells. The flexibility of the method allows for straightforward adaptation to different bacterial species and ... ...

    Abstract In this chapter, we describe in detail how to perform a successful smFISH experiment and how to quantify mRNA transcripts in bacterial cells. The flexibility of the method allows for straightforward adaptation to different bacterial species and experimental conditions. Thanks to the feasibility of the approach, the method can easily be adapted by other laboratories. Finally, we believe that this method has a great potential to generate insights into the complicated life of bacteria.
    MeSH term(s) RNA ; In Situ Hybridization, Fluorescence/methods ; RNA, Messenger/genetics ; Bacteria/genetics
    Chemical Substances RNA (63231-63-0) ; RNA, Messenger
    Language English
    Publishing date 2024-03-19
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3766-1_1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tissue-specific macrophage immunometabolism.

    Ben-Arosh, Hadar / Avraham, Roi

    Current opinion in immunology

    2023  Volume 84, Page(s) 102369

    Abstract: Macrophages are phagocytic cells distributed across tissues that sustain homeostasis by constantly probing their local environment. Upon perturbations, macrophages rewire their energy metabolism to execute their immune programs. Intensive research in the ...

    Abstract Macrophages are phagocytic cells distributed across tissues that sustain homeostasis by constantly probing their local environment. Upon perturbations, macrophages rewire their energy metabolism to execute their immune programs. Intensive research in the field of immunometabolism highlights cell-intrinsic immunometabolites such as succinate and itaconate as immunomodulatory signals. A role for cell-extrinsic stimuli now emerges with evidence for signals that shape macrophages' metabolism in a tissue-specific manner. In this review, we will cover macrophage immunometabolism in the gut, a complex metabolic and immunologically active tissue. During homeostasis, gut macrophages are constantly exposed to pro-inflammatory ligands from the microbiota, and in contrast, are balanced by microbiota-derived anti-inflammatory metabolites. Given their extensive metabolic changes during activation, spatial analyses of the tissue will allow the characterization of metabolic niches of macrophage in the gut. Identifying metabolic perturbations of macrophage subsets during chronic inflammation and infection can direct future tissue-specific metabolotherapies.
    MeSH term(s) Humans ; Macrophages ; Energy Metabolism ; Succinic Acid/metabolism ; Immunity ; Inflammation
    Chemical Substances Succinic Acid (AB6MNQ6J6L)
    Language English
    Publishing date 2023-07-18
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2023.102369
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Dissecting Human Blood Immune Cells Response to Intracellular Infection Using Single-Cell RNA Sequencing.

    Hen-Avivi, Shelly / Avraham, Roi

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2427, Page(s) 133–147

    Abstract: Complex interactions between diverse host immune cells can determine the outcome of pathogen infections. Advances in single-cell RNA sequencing (scRNA-seq) allow detection of the transcriptional patterns of different immune cells at steady state and ... ...

    Abstract Complex interactions between diverse host immune cells can determine the outcome of pathogen infections. Advances in single-cell RNA sequencing (scRNA-seq) allow detection of the transcriptional patterns of different immune cells at steady state and after infection. To reveal the complex interactions of the human immune system in response to diverse intracellular pathogens, we developed a protocol for scRNA-seq of ex vivo infected human peripheral blood mononuclear cells (PBMCs). We demonstrate here infection with Salmonella enterica serovar Typhimurium, but this protocol can be used for any other pathogen of interest, and expand our knowledge of human host-pathogen biology.
    MeSH term(s) Host-Pathogen Interactions/genetics ; Humans ; Leukocytes, Mononuclear ; Salmonella typhimurium/genetics ; Sequence Analysis, RNA/methods
    Language English
    Publishing date 2022-05-26
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1971-1_12
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Immunometabolic crosstalk during bacterial infection.

    Rosenberg, Gili / Riquelme, Sebastian / Prince, Alice / Avraham, Roi

    Nature microbiology

    2022  Volume 7, Issue 4, Page(s) 497–507

    Abstract: Following detection of bacteria, macrophages switch their metabolism from oxidative respiration through the tricarboxylic acid cycle to high-rate aerobic glycolysis. This immunometabolic shift enables pro-inflammatory and antimicrobial responses and is ... ...

    Abstract Following detection of bacteria, macrophages switch their metabolism from oxidative respiration through the tricarboxylic acid cycle to high-rate aerobic glycolysis. This immunometabolic shift enables pro-inflammatory and antimicrobial responses and is facilitated by the accumulation of fatty acids, tricarboxylic acid-derived metabolites and catabolism of amino acids. Recent studies have shown that these immunometabolites are co-opted by pathogens as environmental cues for expression of virulence genes. We review mechanisms by which host immunometabolites regulate bacterial pathogenicity and discuss opportunities for the development of therapeutics targeting metabolic host-pathogen crosstalk.
    MeSH term(s) Bacterial Infections/metabolism ; Citric Acid Cycle ; Humans ; Macrophages/microbiology ; Oxidation-Reduction ; Virulence
    Language English
    Publishing date 2022-04-01
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-022-01080-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Bacterial lifestyle switch in response to algal metabolites.

    Barak-Gavish, Noa / Dassa, Bareket / Kuhlisch, Constanze / Nussbaum, Inbal / Brandis, Alexander / Rosenberg, Gili / Avraham, Roi / Vardi, Assaf

    eLife

    2023  Volume 12

    Abstract: Unicellular algae, termed phytoplankton, greatly impact the marine environment by serving as the basis of marine food webs and by playing central roles in the biogeochemical cycling of elements. The interactions between phytoplankton and heterotrophic ... ...

    Abstract Unicellular algae, termed phytoplankton, greatly impact the marine environment by serving as the basis of marine food webs and by playing central roles in the biogeochemical cycling of elements. The interactions between phytoplankton and heterotrophic bacteria affect the fitness of both partners. It is becoming increasingly recognized that metabolic exchange determines the nature of such interactions, but the underlying molecular mechanisms remain underexplored. Here, we investigated the molecular and metabolic basis for the bacterial lifestyle switch, from coexistence to pathogenicity, in
    MeSH term(s) Phytoplankton/metabolism ; Phytoplankton/microbiology ; Rhodobacteraceae ; Haptophyta
    Language English
    Publishing date 2023-01-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.84400
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Physiological stress drives the emergence of a Salmonella subpopulation through ribosomal RNA regulation.

    Ciolli Mattioli, Camilla / Eisner, Kfir / Rosenbaum, Aviel / Wang, Mengyu / Rivalta, Andre' / Amir, Ariel / Golding, Ido / Avraham, Roi

    Current biology : CB

    2023  Volume 33, Issue 22, Page(s) 4880–4892.e14

    Abstract: Bacteria undergo cycles of growth and starvation to which they must adapt swiftly. One important strategy for adjusting growth rates relies on ribosomal levels. Although high ribosomal levels are required for fast growth, their dynamics during starvation ...

    Abstract Bacteria undergo cycles of growth and starvation to which they must adapt swiftly. One important strategy for adjusting growth rates relies on ribosomal levels. Although high ribosomal levels are required for fast growth, their dynamics during starvation remain unclear. Here, we analyzed ribosomal RNA (rRNA) content of individual Salmonella cells by using fluorescence in situ hybridization (rRNA-FISH) and measured a dramatic decrease in rRNA numbers only in a subpopulation during nutrient limitation, resulting in a bimodal distribution of cells with high and low rRNA content. During nutritional upshifts, the two subpopulations were associated with distinct phenotypes. Using a transposon screen coupled with rRNA-FISH, we identified two mutants, DksA and RNase I, acting on rRNA transcription shutdown and degradation, which abolished the formation of the subpopulation with low rRNA content. Our work identifies a bacterial mechanism for regulation of ribosomal bimodality that may be beneficial for population survival during starvation.
    MeSH term(s) RNA, Ribosomal/genetics ; In Situ Hybridization, Fluorescence ; Ribosomes/metabolism ; Salmonella/genetics ; Salmonella/metabolism ; Stress, Physiological
    Chemical Substances RNA, Ribosomal
    Language English
    Publishing date 2023-10-24
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2023.09.064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book ; Online: GRAM

    Blau, Tsachi / Fogel, Sharon / Ronen, Roi / Golts, Alona / Ganz, Roy / Avraham, Elad Ben / Aberdam, Aviad / Tsiper, Shahar / Litman, Ron

    Global Reasoning for Multi-Page VQA

    2024  

    Abstract: The increasing use of transformer-based large language models brings forward the challenge of processing long sequences. In document visual question answering (DocVQA), leading methods focus on the single-page setting, while documents can span hundreds ... ...

    Abstract The increasing use of transformer-based large language models brings forward the challenge of processing long sequences. In document visual question answering (DocVQA), leading methods focus on the single-page setting, while documents can span hundreds of pages. We present GRAM, a method that seamlessly extends pre-trained single-page models to the multi-page setting, without requiring computationally-heavy pretraining. To do so, we leverage a single-page encoder for local page-level understanding, and enhance it with document-level designated layers and learnable tokens, facilitating the flow of information across pages for global reasoning. To enforce our model to utilize the newly introduced document-level tokens, we propose a tailored bias adaptation method. For additional computational savings during decoding, we introduce an optional compression stage using our C-Former model, which reduces the encoded sequence length, thereby allowing a tradeoff between quality and latency. Extensive experiments showcase GRAM's state-of-the-art performance on the benchmarks for multi-page DocVQA, demonstrating the effectiveness of our approach.
    Keywords Computer Science - Computation and Language ; Computer Science - Computer Vision and Pattern Recognition
    Subject code 004
    Publishing date 2024-01-07
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Breaking the population barrier by single cell analysis: one host against one pathogen.

    Mills, Erez / Avraham, Roi

    Current opinion in microbiology

    2017  Volume 36, Page(s) 69–75

    Abstract: Most of our understanding of the host-bacterium interaction has come from studies of bulk populations. In reality, highly adaptable and dynamic host cells and bacteria engage in complex, diverse interactions. This complexity necessarily limits the depth ... ...

    Abstract Most of our understanding of the host-bacterium interaction has come from studies of bulk populations. In reality, highly adaptable and dynamic host cells and bacteria engage in complex, diverse interactions. This complexity necessarily limits the depth of understanding that can be gained with bulk population measurements. Here, we will review the merit of single cell analysis to characterize this diversity that can trigger heterogeneous outcomes. We will discuss heterogeneity of bacterial and host populations, differences in host microenvironments, technological advances that facilitate the analysis of rare subpopulations, and the potential relevance of these subpopulations to infection outcomes. We focus our discussion on intracellular bacterial pathogens and on methods that characterize and quantify RNA in single cells, aiming to highlight how novel methodologies have the potential to characterize the multidimensional process of infection and to provide answers to some of the most fundamental questions in the field.
    Language English
    Publishing date 2017-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1418474-6
    ISSN 1879-0364 ; 1369-5274
    ISSN (online) 1879-0364
    ISSN 1369-5274
    DOI 10.1016/j.mib.2017.01.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Immune cell type 'fingerprints' at the basis of outcome diversity of human infection.

    Hen-Avivi, Shelly / Avraham, Roi

    Current opinion in microbiology

    2017  Volume 42, Page(s) 31–39

    Abstract: Despite the availability of antibiotics and immunization, infectious diseases remain a major cause of malignancy and death worldwide. Yet, it is well documented that for most infectious agents, clinical disease develops in only a small minority of ... ...

    Abstract Despite the availability of antibiotics and immunization, infectious diseases remain a major cause of malignancy and death worldwide. Yet, it is well documented that for most infectious agents, clinical disease develops in only a small minority of infected individuals. There is, in fact, great heterogeneity in infection outcome, from complete clearance of the pathogen to severe illness. Understanding this variation remains elusive, despite its great potential to equip us with new tools for the treatment of infectious diseases. Here, we propose a novel perspective for studying this diversity in human infection outcome, one that utilizes single-cell analysis technologies. Recent advances in single-cell RNA-seq technologies allow the detection of rare subpopulations that play important roles in host-pathogen interactions. We propose that applying single-cell RNA-seq to the study of infection can provide a 'fingerprint' of the immune cell types that are associated with the ability of the host to clear a pathogen and, thereby, broaden our current understanding of variation in susceptibility to infection within the population.
    MeSH term(s) Anti-Bacterial Agents/adverse effects ; Anti-Bacterial Agents/therapeutic use ; Communicable Diseases/immunology ; Disease Susceptibility/immunology ; Disease Susceptibility/microbiology ; High-Throughput Nucleotide Sequencing/methods ; Host-Pathogen Interactions/immunology ; Humans ; Immune System/cytology ; Single-Cell Analysis/methods
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2017-10-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1418474-6
    ISSN 1879-0364 ; 1369-5274
    ISSN (online) 1879-0364
    ISSN 1369-5274
    DOI 10.1016/j.mib.2017.09.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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