The isochromosome 20q abnormality of pluripotent cells interrupts germ layer differentiation

Chromosome 20 abnormalities are some of the most frequent genomic changes acquired by human pluripotent stem cell (hPSC) cultures worldwide. Yet their effects on differentiation remain largely unexplored. We investigated a recurrent abnormality also found on amniocentesis, the isochromosome 20q (iso20q), during a clinical retinal pigment epithelium differentiation. Here we show that the iso20q abnormality interrupts spontaneous embryonic lineage specification. Isogenic lines revealed that under conditions that promote the spontaneous differentiation of wild-type hPSCs, the iso20q variants fail to differentiate into primitive germ layers and to downregulate pluripotency networks, resulting in apoptosis. Instead, iso20q cells are highly biased for extra-embryonic/amnion differentiation following inhibition of DNMT3B methylation or BMP2 treatment. Finally, directed differentiation protocols can overcome the iso20q block. Our findings reveal in iso20q a chromosomal abnormality that impairs the developmental competency of hPSCs toward germ layers but not amnion, which models embryonic developmental bottlenecks in the presence of aberrations

Effects of grain by-products as supplements for stocker cattle grazing bermudagrass

Two experiments were conducted to compare corn, dried distillers’ grains (DDG), and pelleted soybean hulls (SH) as supplements for cattle grazing bermudagrass. In Exp. 1, 66 crossbred steers (306 ± 3.2 kg) were stratified by weight and allotted randomly to six 2.4-ha bermudagrass pastures for a 107-d study. One of three supplement treatments (corn, DDG, or SH) was assigned randomly to each pasture group and was offered at 0.5% (as fed) of body weight. Calves were weighed at 28-d intervals and supplement was adjusted after each weigh period. In Exp. 2, five ruminally cannulated steers grazed bermudagrass pasture and were individually fed supplements (corn, DDG, or SH) at 0.5% of body weight in a 3 x 3 replicated, incomplete Latin-square design with a 14-d adaptation and a 5-d sampling period. In Exp. 1, supplementation with DDG and corn increased (P \u3c 0.04) the average daily gain compared to supplementation with SH (0.89, 0.87, and 0.74 kg for DDG, corn, and SH, respectively). In Exp. 2, in situ dry-matter-disappearance kinetic measures of bermudagrass were not affected by type of supplementation. The potential extent of digestion for DDG (93%) was lower than for corn (97%, P = 0.01) and SH (96%, P = 0.06). Supplementation with corn or DDG at 0.5% of body weight improved the gain of stocker cattle grazing bermudagrass compared to supplementation with SH, but these differences were not explained by differences in bermudagrass degradation kinetic

Prescribed burning: Spotfires and escapes

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Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Protective Effects of Human iPS-Derived Retinal Pigment Epithelium Cell Transplantation in the Retinal Dystrophic Rat

Transformation of somatic cells with a set of embryonic transcription factors produces cells with the pluripotent properties of embryonic stem cells (ESCs). These induced pluripotent stem (iPS) cells have the potential to differentiate into any cell type, making them a potential source from which to produce cells as a therapeutic platform for the treatment of a wide range of diseases. In many forms of human retinal disease, including age-related macular degeneration (AMD), the underlying pathogenesis resides within the support cells of the retina, the retinal pigment epithelium (RPE). As a monolayer of cells critical to photoreceptor function and survival, the RPE is an ideally accessible target for cellular therapy. Here we report the differentiation of human iPS cells into RPE. We found that differentiated iPS-RPE cells were morphologically similar to, and expressed numerous markers of developing and mature RPE cells. iPS-RPE are capable of phagocytosing photoreceptor material, in vitro and in vivo following transplantation into the Royal College of Surgeons (RCS) dystrophic rat. Our results demonstrate that iPS cells can be differentiated into functional iPS-RPE and that transplantation of these cells can facilitate the short-term maintenance of photoreceptors through phagocytosis of photoreceptor outer segments. Long-term visual function is maintained in this model of retinal disease even though the xenografted cells are eventually lost, suggesting a secondary protective host cellular response. These findings have identified an alternative source of replacement tissue for use in human retinal cellular therapies, and provide a new in vitro cellular model system in which to study RPE diseases affecting human patients