RESUMEN
Vibrio mimicus caused a seafood-associated outbreak in Florida, USA, in which 4 of 6 case-patients were hospitalized; 1 required intensive care for severe diarrhea. Strains were ctx-negative but carried genes for other virulence determinants (hemolysin, proteases, and types I-IV and VI secretion systems). Cholera toxin-negative bacterial strains can cause cholera-like disease.
Asunto(s)
Cólera , Vibrio mimicus , Humanos , Cólera/epidemiología , Florida/epidemiología , Vibrio mimicus/genética , Brotes de Enfermedades , Alimentos MarinosRESUMEN
The switch from precursor cell proliferation to onset of differentiation in adult stem cell lineages must be carefully regulated to produce sufficient progeny to maintain and repair tissues, yet prevent overproliferation that may enable oncogenesis. In the Drosophila male germ cell lineage, spermatogonia produced by germ line stem cells undergo a limited number of transit amplifying mitotic divisions before switching to the spermatocyte program that sets up meiosis and eventual spermatid differentiation. The number of transit amplifying divisions is set by accumulation of the bag-of-marbles (Bam) protein to a critical threshold. In bam mutants, spermatogonia proliferate through several extra rounds of mitosis then die without becoming spermatocytes. Here we show that the key role of Bam for the mitosis to differentiation switch is repressing expression of Held Out Wings (how), homolog of mammalian Quaking. Knock down of how in germ cells was sufficient to allow spermatogonia mutant for bam or its partner benign gonial cell neoplasm (bgcn) to differentiate, while forced expression of nuclear-targeted How protein in spermatogonia wild-type for bam resulted in continued proliferation at the expense of differentiation. Our findings suggest that Bam targets how RNA for degradation by acting as an adapter to recruit the CCR4-NOT deadenylation complex via binding its subunit, Caf40. As How is itself an RNA binding protein with roles in RNA processing, our findings reveal that the switch from proliferation to meiosis and differentiation in the Drosophila male germ line adult stem cell lineage is regulated by a cascade of RNA-binding proteins.
RESUMEN
Proper differentiation of sperm from germline stem cells, essential for production of the next generation, requires dramatic changes in gene expression that drive remodeling of almost all cellular components, from chromatin to organelles to cell shape itself. Here, we provide a single nucleus and single cell RNA-seq resource covering all of spermatogenesis in Drosophila starting from in-depth analysis of adult testis single nucleus RNA-seq (snRNA-seq) data from the Fly Cell Atlas (FCA) study. With over 44,000 nuclei and 6000 cells analyzed, the data provide identification of rare cell types, mapping of intermediate steps in differentiation, and the potential to identify new factors impacting fertility or controlling differentiation of germline and supporting somatic cells. We justify assignment of key germline and somatic cell types using combinations of known markers, in situ hybridization, and analysis of extant protein traps. Comparison of single cell and single nucleus datasets proved particularly revealing of dynamic developmental transitions in germline differentiation. To complement the web-based portals for data analysis hosted by the FCA, we provide datasets compatible with commonly used software such as Seurat and Monocle. The foundation provided here will enable communities studying spermatogenesis to interrogate the datasets to identify candidate genes to test for function in vivo.
Asunto(s)
Células Madre Adultas , Testículo , Animales , Masculino , Testículo/metabolismo , Drosophila , RNA-Seq , SemenRESUMEN
Alternative means for drug delivery are needed to facilitate drug adherence and administration. Microneedles (MNs) have been previously investigated transdermally for drug delivery. To date, drug loading into MNs has been limited by drug solubility in the polymeric blend. We designed a highly drug-loaded MN patch to deliver macromolecules and applied it to the buccal area, which allows for faster delivery than the skin. We successfully delivered 1-mg payloads of human insulin and human growth hormone to the buccal cavity of swine within 30 s. In addition, we conducted a trial in 100 healthy volunteers to assess potential discomfort associated with MNs when applied in the oral cavity, identifying the hard palate as the preferred application site. We envisage that MN patches applied on buccal surfaces could increase medication adherence and facilitate the painless delivery of biologics and other drugs to many, especially for the pediatric and elderly populations.
RESUMEN
The fundamental requirements for regeneration are poorly understood. Planarians can robustly regenerate all tissues after injury, involving stem cells, positional information, and a set of cellular and molecular responses collectively called the "missing tissue" or "regenerative" response. follistatin, which encodes an extracellular Activin inhibitor, is required for the missing tissue response after head amputation and for subsequent regeneration. We found that follistatin is required for the missing tissue response regardless of the wound context, but causes regeneration failure only after head amputation. This head regeneration failure involves follistatin-mediated regulation of Wnt signaling at wounds and is not a consequence of a diminished missing tissue response. All tested contexts of regeneration, including head regeneration, could occur with a defective missing tissue response, but at a slower pace. Our findings suggest that major cellular and molecular programs induced specifically by large injuries function to accelerate regeneration but are dispensable for regeneration itself.