FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations

The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization ( FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( x 1), gastric MALT lymphoma ( x 1) and B-cell non-Hodgkin's lymphoma, not otherwise specified ( x 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene

A Large Human Centrifuge for Exploration and Exploitation Research

This paper addresses concepts regarding the development of an Altered Gravity Platform (AGP) that will serve as a research platform for human space exploration. Space flight causes a multitude of physiological problems, many of which are due to gravity level transitions. Going from Earth’s gravity to microgravity generates fluid shifts, space motion sickness, cardiovascular deconditioning among other changes, and returning to a gravity environment again puts the astronauts under similar stressors. A prolonged stay in microgravity provokes additional deleterious changes such as bone loss, muscle atrophy and loss of coordination or specific psychological stresses. To prepare for future manned space exploration missions, a ground-based research test bed for validating countermeasures against the deleterious effects of g-level transitions is needed. The proposed AGP is a large rotating facility (diameter > 150 m), where gravity levels ranging from 1.1 to 1.5g are generated, covering short episodes or during prolonged stays of weeks or even months. On this platform, facilities are built where a crew of 6 to 8 humans can live autonomously. Adaptation from 1g to higher g levels can be studied extensively and monitored continuously. Similarly, re-adaptation back to 1g, after a prolonged period of altered g can also be investigated. Study of the physiological and psychological adaptation to changing g-levels will provide instrumental and predictive knowledge to better define the ultimate countermeasures that are needed for future successful manned space exploration missions to the Moon, Mars and elsewhere. The AGP initiative will allow scientific experts in Europe and worldwide to investigate the necessary scientific, operational, and engineering inputs required for such space missions. Because so many different physiological systems are involved in adaptation to gravity levels, a multidisciplinary approach is crucial. One of the final and crucial steps is to verify the AGP concept through a large scientific community through feedback from various scientific societies. This facility will also serve clinical research on Earth, because a multitude of health problems such as osteoporosis, frailty of the elderly, inactivity, sarcopenia, obesity, insulin resistance and diabetes, cardiovascular problems, connective tissue ageing and immune deficiency, among others stand to benefit from the fundamental insights into the effects of our ever-present terrestrial gravity gained with such a novel research platform