Transposon-encoded CRISPR-Cas systems direct RNA-guided DNA integration.

Conventional CRISPR-Cas systems maintain genomic integrity by leveraging guide RNAs for the nuclease-dependent degradation of mobile genetic elements, including plasmids and viruses. Here we describe a notable inversion of this paradigm, in which bacterial Tn7-like transposons have co-opted nuclease-deficient CRISPR-Cas systems to catalyse RNA-guided integration of mobile genetic elements into the genome. Programmable transposition of Vibrio cholerae Tn6677 in Escherichia coli requires CRISPR- and transposon-associated molecular machineries, including a co-complex between the DNA-targeting complex Cascade and the transposition protein TniQ. Integration of donor DNA occurs in one of two possible orientations at a fixed distance downstream of target DNA sequences, and can accommodate variable length genetic payloads. Deep-sequencing experiments reveal highly specific, genome-wide DNA insertion across dozens of unique target sites. This discovery of a fully programmable, RNA-guided integrase lays the foundation for genomic manipulations that obviate the requirements for double-strand breaks and homology-directed repair.

[Uveitis: late complication of undiagnosed Whipple disease]. / Uvéite: complication tardive d'une maladie de Whipple méconnue.

We report a case of severe chronic bilateral uveitis in a 60-year-old white man without neurological manifestations. Spondylarthritis and isolated malabsorption suggested the diagnosis of Whipple's disease. A normal duodenal biopsy delated the diagnosis, who was secondarily demonstrated an adenopathy biopsy and macrophage study on vitrectomy sample (macrophage distended by periodic acid-Schiff positive material). With 1 year follow-up the uveitis was rapidly and completely cured by an antibiotic association (rifampicin and trimethoprim-sulfamethoxazol). The characteristics of ocular involvement in Whipple's disease and treatment of the disease are discussed.

Morphology of primate's dopaminergic amacrine cells as revealed by TH-like immunoreactivity on retinal flat-mounts.

Dopaminergic (DA) cells have been revealed by immunohistochemical localization of tyrosine hydroxylase in the retina of cynomolgus monkey, chimpanzee and human. The DA neurons were visualized in cross-sections as well as in flat-mounts of retina. The comparison revealed a striking morphological similarity between the DA neurons in the three species. When observed in flat-mounts, they were of stellate type; when observed in cross-sections, except for a few displaced cells, they were unistratified amacrine cells branching in the outermost sublayer of the inner plexiform layer. Observations in sections suggested the existence of DA-interplexiform cells in ape and human retinas.

Thymic involution in pregnant mice. II. Functional aspects of the remaining thymocytes.

Non-specific immunological modifications in mice during syngeneic gestation can be demonstrated. A dramatic transient thymic involution results from a significant reduction in the subpopulations of the thymic cortex with the remaining thymocytes being mainly medullary in nature. Response to PHA and Con A is greatly reduced in this pool which can normally be strongly stimulated. No suppressor cells or alteration in thymic epithelial function could be demonstrated. The unexpected low responsiveness of the remaining thymocytes was reversible after in vitro neuraminidase treatment. Meanwhile, MRL of thymocytes to allogeneic cell during syngenic gestation was not impaired.

Thymic involution in pregnant mice. I. Characterization of the remaining thymocyte subpopulations.

Pregnancy-induced thymic atrophy was studied in mice during the course of syngeneic gestation and the post-partum period. Cortical thymocytes were greatly reduced in number as shown by the binding of fluorescein-labelled PNA. The pool of steroid-resistant (SR) medullary thymocytes appeared unchanged in pregnant mice when studied by means of a specific heteroantiserum (SRCA). Therefore, in pregnant mice, these two surface markers demonstrated that thymic atrophy was linked to steroid-sensitive (SS) cortical cell reduction. The presumed hydrocortisone resistance of the mother's remaining thymocytes is not related to a difference in the number of steroid receptors as determined by 3H-dexamethasone binding.

Aniridia, male pseudohermaphroditism, gonadoblastoma, mental retardation, and del 11p13.

A 20-month-old male patient was referred because of severe growth and mental retardation, bilateral glaucoma, hypospadias, and cryptorchidism. Karyotyping revealed a de novo complex three-chromosome rearrangement as well as deletion of band 11p13:46,XY,t(4;7;15)(q212;p14;q26)del(11)(p13p14). Trabeculectomia revealed bilateral aniridia. Surgery on the genitalia revealed male pseudohermaphroditism and bilateral gonadoblastoma. The kidneys were normal. A deficiency in catalase (CAT) activity allowed the regional assignment of the CAT gene to band 11p13.

[Experimental uveoretinitis induced in monkeys by retinal S antigen. Induction, histopathology (author's transl)]. / Uvéo-rétinite expérimentale induite par l'antigène S rétinien chez le singe. Induction, histopathologie.

S antigen was isolated from human and bovine retinas and purified by two chromatographic steps. Its purity was controlled by SDS-electrophoresis and immunodiffusion. Seven Cynomolgus monkeys received a single subcutaneous immunization with either 50 or 100 micrograms of human S antigen (5 animals) or 100 micrograms of bovine S antigen (2 animals) with complete Freund's adjuvant. All the monkeys had bilateral uveoretinitis and anti-"S" antibodies were found in their serum. The time course of the disease was followed clinically during one year and pathologic features were described at various time intervals. The disease includes prominent retinal vasculitis and granulomatous chorio-retinitis, with a chronic course, and leads after many months to almost complete destruction of the retina, with persistence of inflammatory infiltrates and pigment of cell migration.