Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression

Hepcidin is a key regulator of systemic iron homeostasis. Hepcidin deficiency induces iron overload, whereas hepcidin excess induces anemia. Mutations in the gene encoding hemojuvelin (HFE2, also known as HJV) cause severe iron overload and correlate with low hepcidin levels, suggesting that hemojuvelin positively regulates hepcidin expression. Hemojuvelin is a member of the repulsive guidance molecule (RGM) family, which also includes the bone morphogenetic protein (BMP) coreceptors RGMA and DRAGON (RGMB). Here, we report that hemojuvelin is a BMP coreceptor and that hemojuvelin mutants associated with hemochromatosis have impaired BMP signaling ability. Furthermore, BMP upregulates hepatocyte hepcidin expression, a process enhanced by hemojuvelin and blunted in Hfe2-/- hepatocytes. Our data suggest a mechanism by which HFE2 mutations cause hemochromatosis: hemojuvelin dysfunction decreases BMP signaling, thereby lowering hepcidin expression.     

Night shift paralysis

12% of night nurses surveyed claimed to have suffered from a totally incapacitating paralysis that may be related to sleep paralysis, and contribute to impaired levels of safety on the night shift. The incidence of this paralysis is shown to be age-related, largely confined to the early hours of the morning, and to increase over consecutive night shifts.     

Genomic screening and replication using the same data set in family-based association testing

The Human Genome Project and its spin-offs are making it increasingly feasible to determine the genetic basis of complex traits using genome-wide association studies. The statistical challenge of analyzing such studies stems from the severe multiple-comparison problem resulting from the analysis of thousands of SNPs. Our methodology for genome-wide family-based association studies, using single SNPs or haplotypes, can identify associations that achieve genome-wide significance. In relation to developing guidelines for our screening tools, we determined lower bounds for the estimated power to detect the gene underlying the disease-susceptibility locus, which hold regardless of the linkage disequilibrium structure present in the data. We also assessed the power of our approach in the presence of multiple disease-susceptibility loci. Our screening tools accommodate genomic control and use the concept of haplotype-tagging SNPs. Our methods use the entire sample and do not require separate screening and validation samples to establish genome-wide significance, as population-based designs do.     

Autoradiographic demonstration of estrogen uptake by the armadillo pituitary gland

Summary Adult female armadillos were injected with tritiated estradiol. The pituitary gland was removed and processed for autoradiography. Nuclear uptake and retention of the steroid was found in 28.8% of the cells in the pars distalis and 3.7% of the pituicytes.This study was supported in part by USPHS Research Career Development Award NS 00164 (PJS) and USPHS Grants NS 12933, HD 10914, HD 10202, and RR 07187.     

Molecular basis of morphogenesis during vertebrate gastrulation

Gastrulation is a crucial step in early embryogenesis. During gastrulation, a set of morphogenetic processes takes place leading to the establishment of the basic body plan and formation of primary germ layers. A rich body of knowledge about these morphogenetic processes has been accumulated over decades. The understanding of the molecular mechanism that controls the complex cell movement and inductive processes during gastrulation remains a challenge. Substantial progress has been made recently to identify and characterize pathways and molecules implicated in the modulation of morphogenesis during vertebrate gastrulation. Here, we summarize recent findings in the analysis of signaling pathways implicated in gastrulation movements, with the aim to generalize the basic molecular principles of vertebrate morphogenesis.     

Selection of a Representative Sample

Sometimes a larger dataset needs to be reduced to just a few points, and it is desirable that these points be representative of the whole dataset. If the future uses of these points are not fully specified in advance, standard decision-theoretic approaches will not work. We present here methodology for choosing a small representative sample based on a mixture modeling approach.