Cytogenetic studies of early myeloid progenitor compartments in Ph<SUP>1</SUP>- positive chronic myeloid leukemia. II. Long-term culture reveals the persistence of Ph<SUP>1</SUP>-negative progenitors in treated as well as newly diagnosed patients

We recently showed that long-term marrow cultures can be used to demonstrate the presence of Philadelphia (Ph1) negative progenitors in patients with newly diagnosed Ph1-positive chronic myeloid leukemia (CML). We now report results for 6 chronic phase patients studied 5-83 mo postdiagnosis and an additional 3 newly diagnosed patients. Marrow metaphases were exclusively Ph1-positive. Clonogenic assays revealed a minor population of Ph1-negative progenitors in 3 cases (1 treated, 2 untreated). Long-term marrow culture adherent layers contained Ph1- negative progenitors in 6 cases (3 treated, 3 untreated). Whenever this occurred, the Ph1-negative population had become the only one detectable within 3-4 wk, and this was always associated with a rapid decline of the Ph1-positive population. For 2 of the 3 cases where Ph1- negative progenitors were not detected, there was a similar rapid decline in the Ph1-positive population in culture. In the other case, Ph1-positive progenitors were maintained at levels typically seen in normal long-term marrow cultures. These results suggest that chromosomally normal stem cells may persist for a considerable period in the marrow of some, but perhaps not all, patients with CML, even in the face of maintenance chemotherapy. In addition, they provide new evidence of heterogeneity in this disease, as shown by the variable ability of Ph1-positive progenitor populations to be maintained in vitro

Towards a Standard Approach for Wear Testing of Wheel and Rail Materials

Examination of the literature for wear testing methodologies for wheel and rail material reveals that while only a few different techniques have been used there is a wide variety in exactly how the tests have been conducted and the resulting data reported. This makes comparison of the data very difficult. This work, carried out as part of the International Collaborative Research Initiative (ICRI) which is aiming to bring together wheel/rail interface researchers from across the world to collate data and knowledge to try to solve some of the common problems that are faced, has examined the different approaches used and attempted to pull together all the good practice used into a test specification for future twin disc testing for wheel and rail materials. Adoption of the method will allow data to be compared reliably and eventually enable data to be compiled into wear maps to use as input, for example, to multi-body dynamics simulation wear prediction tools

Strigolactones inhibit auxin feedback on PIN-dependent auxin transport canalization

Directional transport of the phytohormone auxin is a versatile, plant-specific mechanism regulating many aspects of plant development. The recently identified plant hormones, strigolactones (SLs), are implicated in many plant traits; among others, they modify the phenotypic output of PIN-FORMED (PIN) auxin transporters for fine-tuning of growth and developmental responses. Here, we show in pea and Arabidopsis that SLs target processes dependent on the canalization of auxin flow, which involves auxin feedback on PIN subcellular distribution. D14 receptor- and MAX2 F-box-mediated SL signaling inhibits the formation of auxin-conducting channels after wounding or from artificial auxin sources, during vasculature de novo formation and regeneration. At the cellular level, SLs interfere with auxin effects on PIN polar targeting, constitutive PIN trafficking as well as clathrin-mediated endocytosis. Our results identify a non-transcriptional mechanism of SL action, uncoupling auxin feedback on PIN polarity and trafficking, thereby regulating vascular tissue formation and regeneration