Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells

Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.     

Structural comparison of urease and a GroEL analog from Helicobacter pylori.

Electron microscopy of purified protein preparations indicated that Helicobacter pylori urease consisted of circular particles that are 13 nm in diameter, some of which showed indications of threefold rotational symmetry. A GroEL analog of H. pylori (Hp60K) appeared as a disc-shaped molecule with a diameter similar to that of urease but possessed sevenfold rotational symmetry. In a side-view projection, Hp60K appeared as two or four discs stacked side by side.     

In Vivo Detection of Human TRPV6-Rich Tumors with Anti-Cancer Peptides Derived from Soricidin

Soricidin is a 54-amino acid peptide found in the paralytic venom of the northern short-tailed shrew (Blarina brevicauda) and has been found to inhibit the transient receptor potential of vallinoid type 6 (TRPV6) calcium channels. We report that two shorter peptides, SOR-C13 and SOR-C27, derived from the C-terminus of soricidin, are high-affinity antagonists of human TRPV6 channels that are up-regulated in a number of cancers. Herein, we report molecular imaging methods that demonstrate the in vivo diagnostic potential of SOR-C13 and SOR-C27 to target tumor sites in mice bearing ovarian or prostate tumors. Our results suggest that these novel peptides may provide an avenue to deliver diagnostic and therapeutic reagents directly to TRPV6-rich tumors and, as such, have potential applications for a range of carcinomas including ovarian, breast, thyroid, prostate and colon, as well as certain leukemia''s and lymphomas.     

Persistent and heritable structural damage induced in heterochromatic DNA from rat liver by N-nitrosodimethylamine

Analysis, by benzoylated DEAE-cellulose chromatography, has been made of structural change in eu- and heterochromatic DNA from rat liver following administration of the carcinogen N-nitrosodimethylamine (10 mg/kg body weight). Either hepatic DNA was prelabeled with [3H]thymidine administered 2-3 weeks before injection of the carcinogen or the labeled precursor was given during regenerative hyperplasia in rats treated earlier with N-nitrosodimethylamine. Following phenol extraction of either whole liver homogenate or nuclease-fractionated eu- and heterochromatin, carcinogen-modified DNA was examined by stepwise or caffeine gradient elution from benzoylated DEAE-cellulose. In whole DNA, nitrosamine-induced single-stranded character was maximal 4-24 h after treatment, declining rapidly thereafter; gradient elution of these DNA preparations also provided short-term evidence of structural change. Following incubation of purified nuclei with micrococcal nuclease, 10-12% of labeled DNA was solubilized (eu-chromatin) by 1.0 unit of micrococcal nuclease (5 mg of DNA)-1 mL-1 after 9 min. In prelabeled animals, administration of N-nitrosodimethylamine caused a marked fall in the specific radioactivity of solubilized DNA, while that of sedimenting DNA was not affected. Caffeine gradient chromatography suggested short-term nitrosamine-induced structural change in euchromatic DNA, while increased binding of heterochromatic DNA was evident for up to 3 months after carcinogen treatment. Preparations of newly synthesized heterochromatic DNA from animals subjected to hepatectomy up to 2 months after carcinogen treatment provided evidence of heritable structural damage. Carcinogen-induced binding of heterochromatic DNA to benzoylated DEAE-cellulose was indicative of specific structural lesions whose affinity equalled that of single-stranded DNA up to 1.0 kilobase in length.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in severity of myocardial infarction and three year survival rates after myocardial infarction in Auckland, 1966-7 and 1981-2.

Mortality from coronary heart disease has been declining steadily over the past 20 years in Auckland. The possibility that improved survival contributed to this decline was examined in patients who survived four weeks after myocardial infarction, changes in the severity of the disease being controlled for. Patients who had had myocardial infarction in 1966-7 (191 patients) or 1981-2 (203) were compared to determine whether three year survival rates had changed and the severity of the disease altered. With a coronary prognostic index taken as the measure of severity the 1981-2 group had significantly more severe myocardial infarctions than the 1966-7 group, but despite this the three year survival was significantly better (86% in the 1981-2 group v 75% in the 1966-7 group). These findings suggest that improved survival after myocardial infarction contributed to the decline in mortality.     

Cogwheel: A physician's view of a local version

A preliminary experiment in the divisional system of medical administration has been started in a large regional hospital in the Metropolitan area. This has involved considerable local interpretation of the original proposals in the Joint Working Party''s report. The chief benefits of this version as tried so far have been a more effective use of doctors'' time at all levels, a more rapid carrying out of practical suggestions, and closer co-operation between different departments. Those who give first administrative place to streamlined efficiency have seen the absence of an authoritative executive committee as the chief defect to date. The main fault in the eyes of those who emphasize the fundamental importance of participation has been the delay in the involvement of the junior medical staff.