High NRBP1 expression in prostate cancer is linked with poor clinical outcomes and increased cancer cell growth

We recently established the rationale that NRBP1 (nuclear receptor binding protein 1) has a potential growth-promoting role in cell biology. NRBP1 interacts directly with TSC-22, a potential tumor suppressor gene that is differently expressed in prostate cancer. Consequently, we analyzed the role of NRBP1 expression in prostate cancer cell lines and its expression on prostate cancer tissue microarrays (TMA).

Io volcano observer (IVO) integrated approach to optimizing system design for radiation challenges

One of the major challenges for a mission to the Jovian system is the radiation tolerance of the spacecraft (S/C) and the payload. Moreover, being able to achieve science observations with high signal to noise ratios (SNR), while passing through the high flux radiation zones, requires additional ingenuity on the part of the instrument provider. Consequently, the radiation mitigation is closely intertwined with the payload, spacecraft and trajectory design, and requires a systems-level approach. This paper presents a design for the Io Volcano Observer (IVO), a Discovery mission concept that makes multiple close encounters with Io while orbiting Jupiter. The mission aims to answer key outstanding questions about Io, especially the nature of its intense active volcanism and the internal processes that drive it. The payload includes narrow-angle and wide-angle cameras (NAC and WAC), dual fluxgate magnetometers (FGM), a thermal mapper (ThM), dual ion and neutral mass spectrometers (INMS), and dual plasma ion analyzers (PIA). The radiation mitigation is implemented by drawing upon experiences from designs and studies for missions such as the Radiation Belt Storm Probes (RBSP) and Jupiter Europa Orbiter (JEO). At the core of the radiation mitigation is IVO's inclined and highly elliptical orbit, which leads to rapid passes through the most intense radiation near Io, minimizing the total ionizing dose (177 krads behind 100 mils of Aluminum with radiation design margin (RDM) of 2 after 7 encounters). The payload and the spacecraft are designed specifically to accommodate the fast flyby velocities (e.g. the spacecraft is radioisotope powered, remaining small and agile without any flexible appendages). The science instruments, which collect the majority of the high-priority data when close to Io and thus near the peak flux, also have to mitigate transient noise in their detectors. The cameras use a combination of shielding and CMOS detectors with extremely fast readout to mi- imize noise. INMS microchannel plate detectors and PIA channel electron multipliers require additional shielding. The FGM is not sensitive to noise induced by energetic particles and the ThM microbolometer detector is nearly insensitive. Detailed SNR calculations are presented. To facilitate targeting agility, all of the spacecraft components are shielded separately since this approach is more mass efficient than using a radiation vault. IVO uses proven radiation-hardened parts (rated at 100 krad behind equivalent shielding of 280 mils of Aluminum with RDM of 2) and is expected to have ample mass margin to increase shielding if needed.

A KEL gene encoding serine at position 193 of the Kell glycoprotein results in expression of KEL1 antigen

BACKGROUND: The KEL2/KEL1 (k/K) blood group polymorphism represents 578C>T in the KEL gene and Thr193Met in the Kell glycoprotein. Anti-KEL1 can cause severe hemolytic disease of the fetus and newborn. Molecular genotyping for KEL*1 is routinely used for assessing whether a fetus is at risk. Red blood cells (RBCs) from a KEL:1 blood donor (D1) were found to have abnormal KEL1 expression during evaluation of anti-KEL1 reagents. STUDY DESIGN AND METHODS: Kell genotyping methods, including KEL exon 6 direct sequencing, were applied. KEL cDNA from D1 was sequenced. Flow cytometry was used to assess KEL1 and KEL2 RBC expression. RESULTS: RBCs from the donor, her mother, and an unrelated donor gave weak or negative reactions with some anti-KEL1 reagents. Other Kell-system antigens appeared normal. The three individuals were homozygous for KEL C578 (KEL*2) but heterozygous for a 577A>T transversion, encoding Ser193. They appeared to be KEL*2 homozygotes by routine genotyping methods. Flow cytometry revealed weak KEL1 expression and normal KEL2, similar to that of KEL*2 homozygotes. CONCLUSION: Ser193 in the Kell glycoprotein appears to result in expression of abnormal KEL1, in addition to KEL2. The mutation is not detected by routine Kell genotyping methods and, because of unpredicted KEL1 expression, could lead to a misdiagnosis.

Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes

BACKGROUND: Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients. METHODS: We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons. RESULTS: We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1x10(-7)). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies. CONCLUSIONS: We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype.