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A hyperpromiscuous antitoxin protein domain for the neutralization of diverse toxin domains

Toxin-antitoxin (TA) gene pairs are ubiquitous in microbial chromosomal genomes and plasmids as well as temperate bacteriophages. They act as regulatory switches, with the toxin limiting the growth of bacteria and archaea by compromising diverse essential cellular targets and the antitoxin counteracting the toxic effect. To uncover previously uncharted TA diversity across microbes and bacteriophag

In vitro biomimetic engineering of a human hematopoietic niche with functional properties

In adults, human hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment. Our understanding of human hematopoiesis and the associated niche biology remains limited, due to human material accessibility and limits of existing in vitro culture models. The establishment of an in vitro BM system would offer an experimentally accessible and tunable platform to stu

Engineered humanized bone organs maintain human hematopoiesis in vivo

Hematopoietic stem cells (HSCs) are maintained in a specialized bone marrow (BM) environment, the so-called HSC niche, that provides pivotal factors for their maintenance. Although the cellular and molecular components of the mouse BM HSC niche have been extensively studied using genetically modified animals, relatively little is known about the counterpart human BM niche components. We previously

Mouse and human HSPC immobilization in liquid culture by CD43- or CD44-antibody coating

Keeping track of individual cell identifications is imperative to the study of dynamic single-cell behavior over time. Highly motile hematopoietic stem and progenitor cells (HSPCs) migrate quickly and do not adhere, and thus must be imaged very frequently to keep cell identifications. Even worse, they are also flushed away during medium exchange. To overcome these limitations, we tested antibody c

Engineered extracellular matrices as biomaterials of tunable composition and function

Engineered and decellularized extracellular matrices (ECM) are receiving increasing interest in regenerative medicine as materials capable to induce cell growth/differentiation and tissue repair by physiological presentation of embedded cues. However, ECM production/decellularization processes and control over their composition remain primary challenges. This study reports engineering of ECM mater

Fat-Derived Stromal Vascular Fraction Cells Enhance the Bone-Forming Capacity of Devitalized Engineered Hypertrophic Cartilage Matrix

Engineered and devitalized hypertrophic cartilage (HC) has been proposed as bone substitute material, potentially combining the features of osteoinductivity, resistance to hypoxia, capacity to attract blood vessels, and customization potential for specific indications. However, in comparison with vital tissues, devitalized HC grafts have reduced efficiency of bone formation and longer remodeling t

Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis.

The role of cell-free extracellular matrix (ECM) in triggering tissue and organ regeneration has gained increased recognition, yet current approaches are predominantly based on the use of ECM from fully developed native tissues at nonhomologous sites. We describe a strategy to generate customized ECM, designed to activate endogenous regenerative programs by recapitulating tissue-specific developme

Combination of immortalization and inducible death strategies to generate a human mesenchymal stromal cell line with controlled survival

The hTERT-immortalization of human bone marrow-derived Mesenchymal Stromal Cells (hMSCs) was proposed to address availability/standardization issues for experimental or clinical studies, but raised concerns due to possible uncontrolled growth or malignant cell transformation. Here we report a method to generate a hMSCs line with controlled survival, through the implementation of a pre-established

Tissue decellularization by activation of programmed cell death

Decellularized tissues, native or engineered, are receiving increasing interest in the field of regenerative medicine as scaffolds or implants for tissue and organ repair. The approach, which offers the opportunity to deliver off-the-shelf bioactive materials without immuno-matching requirements, is based on the rationale that extracellular matrix (ECM)-presented cues can be potently instructive t

Engineering of a functional bone organ through endochondral ossification

Embryonic development, lengthening, and repair of most bones proceed by endochondral ossification, namely through formation of a cartilage intermediate. It was previously demonstrated that adult human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) can execute an endochondral program and ectopically generate mature bone. Here we hypothesized that hMSCs pushed through endochondral ossifi

Engineering Human Bone Marrow Proxies

Recent advances in engineering complex organs in vitro inspire the development of human bone marrow equivalents to foster scientific discovery and innovative therapeutics. Here, we discuss challenges in generating relevant human bone marrow proxies, potential design principles, and future directions.

Engineered decellularized matrices to instruct bone regeneration processes.

Despite the significant progress in the field of bone tissue engineering, cell-based products have not yet reached the stage of clinical adoption. This is due to the uncertain advantages from the standard-of-care, combined with challenging cost-and regulatory-related issues. Novel therapeutic approaches could be based on exploitation of the intrinsic regenerative capacity of bone tissue, provided

Delivery of cellular factors to regulate bone healing

Bone tissue has a strong intrinsic regenerative capacity, thanks to a delicate and complex interplay of cellular and molecular processes, which tightly involve the immune system. Pathological settings of anatomical, biomechanical or inflammatory nature may lead to impaired bone healing. Innovative strategies to enhance bone repair, including the delivery of osteoprogenitor cells or of potent cytok

Confluences of Street Culture and Jihadism : The spatial, bodily, and narrative dimensions of radicalization

Research on the new crime-terror nexus has focused on examining the confluences of criminal and jihadist milieus. This article contributes to this research, using insights from criminological theory and analyzing data from interviews with Muslim men who have been exposed to jihadism and have a background in street life and crime. We propose that the connection between street crime and jihadism can

Phosphorylation of the Saccharomyces cerevisiae La protein does not appear to be required for its functions in tRNA maturation and nascent RNA stabilization

An abundant nuclear phosphoprotein, the La autoantigen, is the first protein to bind all newly synthesized RNA polymerase III transcripts. Binding by the La protein to the 3′ ends of these RNAs stabilizes the nascent transcripts from exonucleolytic degradation. In the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, the La protein is required for the normal pathway of tRNA maturation

The La protein

Ubiquitous in eukaryotic cells, the La protein associates with the 3′ termini of many newly synthesized small RNAs. RNAs bound by the La protein include all nascent transcripts made by RNA polymerase III as well as certain small RNAs synthesized by other RNA polymerases. Recent genetic and biochemical analyses have revealed that binding by the La protein protects the 3′ ends of these RNAs from exo

A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen

Antibodies against a conserved RNA-binding protein, the Ro 60-kDa autoantigen, occur in 24–60% of all patients with systemic lupus erythematosus. Anti-Ro antibodies are correlated with photosensitivity and cutaneous lesions in these patients and with neonatal lupus, a syndrome in which mothers with anti-Ro antibodies give birth to children with complete congenital heart block and photosensiti

"The maize is the cost of the farming, and cassava is our profit": Smallholders' perceptions and attitudes to poor crop patches in the Eastern region of Ghana

BackgroundCrop yields are lowest in sub-Saharan Africa compared to other regions, and this is true even for such an important staple crop as maize. Persistence of patches of low crop vigour side-by-side to patches with healthier maize crops has been shown to significantly contribute to low yields on smallholdings. Farmers' perspectives on the presence of such poor patches are important as far as t

Orthotopic Bone Formation by Streamlined Engineering and Devitalization of Human Hypertrophic Cartilage

Most bones of the human body form and heal through endochondral ossification, whereby hypertrophic cartilage (HyC) is formed and subsequently remodeled into bone. We previously demonstrated that HyC can be engineered from human mesenchymal stromal cells (hMSC), and subsequently devitalized by apoptosis induction. The resulting extracellular matrix (ECM) tissue retained osteoinductive properties, l