Lennart Philipson (1929-2011): A Warrior Has Passed Obituary

Lennart Philipson died on June 26, 2011. His passing is a great loss to the worldwide biomedical research community. He was a big man—physically, emotionally and operationally, dominating rooms, psyches and institutions. He was my wonderful friend, and when Lennart became your friend, it filled a big need in your life

Presidential address : a global perspective on science and technology

The United States is a huge ocean-flanked country that, since World War II, has led the world in the development of science and technology. But other countries are now catching up. The American Association for the Advancement of Science (AAAS) has been a support for the development of American science since the 19th century, but as the rest of the world becomes increasingly relevant, it has chosen to expand its purview to become more of an international friend of science. At the 174th annual meeting of the AAAS, we chose to reflect this new perspective

The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules

The inflammatory response plays out over time in a reproducible and organized way after an initiating stimulus. Here we show that genes activated in cultured mouse fibroblasts in response to the cytokine tumor necrosis factor could be categorized into roughly three groups, each with different induction kinetics. Although differences in transcription were important in determining the grouping of these genes, differences in mRNA stability also exerted a strong influence on the temporal order of gene expression, in some cases overriding that of transcriptional control elements. Transcripts of mRNA expressed early had abundant AU-rich elements in their 3' untranslated regions, whereas those expressed later had fewer. Thus, mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of gene expression induced by proinflammatory cytokines

The effect of helper virus on Abelson virus-induced transformation of lymphoid cells

Abelson murine leukemia virus (A-MuLV)-transformed fibroblast nonproducer cells were used to prepare A-MuLV stocks containing a number of different helper viruses. The oncogenicity of the A-MuLV stocks was tested by animal inoculation and their ability to transform normal mouse bone marrow cells was measured in vitro. All of the A-MuLV stocks transformed fibroblast cells efficiently. However, only A-MuLV stocks prepared with helper viruses that are highly oncogenic were efficient in vivo and in vitro in hematopoietic cell transformation. In addition, inefficient helpers did not establish a stable infection in lymphoid nonproducer cells. Thus, helper virus has a more central role in lymphoid cell transformation than in fibroblast cell transformation

Circuitry of nuclear factor κB signaling

Over the past few years, the transcription factor nuclear factor (NF)-κB and the proteins that regulate it have emerged as a signaling system of pre-eminent importance in human physiology and in an increasing number of pathologies. While NF-κB is present in all differentiated cell types, its discovery and early characterization were rooted in understanding B-cell biology. Significant research efforts over two decades have yielded a large body of literature devoted to understanding NF-κB's functioning in the immune system. NF-κB has been found to play roles in many different compartments of the immune system during differentiation of immune cells and development of lymphoid organs and during immune activation. NF-κB is the nuclear effector of signaling pathways emanating from many receptors, including those of the inflammatory tumor necrosis factor and Toll-like receptor superfamilies. With this review, we hope to provide historical context and summarize the diverse physiological functions of NF-κB in the immune system before focusing on recent advances in elucidating the molecular mechanisms that mediate cell type-specific and stimulus-specific functions of this pleiotropic signaling system. Understanding the genetic regulatory circuitry of NF-κB functionalities involves system-wide measurements, biophysical studies, and computational modeling

Purification and properties of a HeLa cell enzyme able to remove the 5'- terminal protein from poliovirus RNA

Using a rapid phenol extraction assay, an enzyme was purified from uninfected HeLa cells that can cleave the 5'-terminal protein (VPg) from poliovirus RNA. Both cytoplasmic and nuclear extracts had enzymes with similar behavior. A polypeptide of molecular weight 27,000 was the major one present in the purified preparation. Assuming that this protein is the enzyme, a very low turnover number was calculated for it. The purified enzyme would cleave the tyrosine-phosphate bond linking VPg to poliovirus RNA with minimal degradation of the RNA or of VPg. If the RNA was first treated with proteinase K to degrade VPg, leaving a small peptide on the RNA, this peptide could also be removed by the enzyme. If the RNA was degraded with T1 RNase, leaving VPg attached to a nonanucleotide, the enzyme still would cleave off VPg, although incompletely. If the RNA was degraded completely, leaving either pUp or pU attached to VPg, the enzyme would not remove the nucleotides from the protein. Thus, for the enzyme to be active requires some length of polynucleotide attached to the protein but only a short peptide need be present for the enzyme to act