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1081. Double identity for proteins of the Bcl-2 family.
Bcl-2 is an oncogenic protein that acts by inhibiting programmed cell death. The mechanisms used by this and related anti-apoptotic proteins to protect cells from cytotoxic stimuli are now emerging, with the discovery that Bcl-2 can function both as an ion channel and as an adaptor or docking protein.
1082. Signalling through the lipid products of phosphoinositide-3-OH kinase.
When a stimulatory agonist molecule binds at the exterior of the cell membrane, a second messenger transduces the signal to the interior of the cell. Second messengers can be derived from phospholipids in the membrane by the action of the enzymes phospholipase C or phosphoinositide-3-OH kinase (PI(3)K). PI(3)K is a key player in many cellular responses, including the movement of organelle membranes, shape alteration through rearrangement of cytoskeletal actin, transformation and chemotaxis. But how PI(3)K mediates these responses is only now becoming clear.
1083. Functional rafts in cell membranes.
A new aspect of cell membrane structure is presented, based on the dynamic clustering of sphingolipids and cholesterol to form rafts that move within the fluid bilayer. It is proposed that these rafts function as platforms for the attachment of proteins when membranes are moved around inside the cell and during signal transduction.
1084. Nucleocytoplasmic transport: signals, mechanisms and regulation.
In eukaryotic organisms, DNA replication and RNA biogenesis occur in the cell nucleus, whereas protein synthesis occurs in the cytoplasm. Integration of these activities depends on selective transport of proteins and ribonucleoprotein particles between the two compartments. Transport across the nuclear envelope occurs through large multiprotein structures, termed nuclear pore complexes. It is signal-mediated and requires both energy and soluble factors, including shuttling carriers. Here I summarize current understanding of nucleocytoplasmic transport and illustrate the importance of regulated transport for signal transduction.
1085. Mechanisms of angiogenesis.
After the developing embryo has formed a primary vascular plexus by a process termed vasculogenesis, further blood vessels are generated by both sprouting and non-sprouting angiogenesis, which are progressively pruned and remodelled into a functional adult circulatory system. Recent results, particularly from the study of mice lacking some of the signalling systems involved, have greatly improved our understanding of the molecular basis underlying these events, and may suggest new approaches for treating conditions such as cancer that depend on angiogenesis.
1086. Transcriptional activation by recruitment.
The recruitment model for gene activation stipulates that an activator works by bringing the transcriptional machinery to the DNA. Recent experiments in bacteria and yeast indicate that many genes can be activated by this mechanism. These findings have implications for our understanding of the nature of activating regions and their targets, and for the role of histones in gene regulation.
1087. Host factors and the pathogenesis of HIV-induced disease.
The level of human immunodeficiency virus (HIV) replication in patients reflects a balance between stimulatory and inhibitory host factors (particularly endogenous cytokines). New information concerning the cellular co-receptors for HIV and the cellular tropism of different strains of virus will advance our understanding of HIV-induced pathogenesis and suggests new therapeutic and preventive strategies.
1089. For medicinal purposes.
Developments in techniques of pharmaceutical chemistry are poised to revolutionize the design of drugs beyond previous expectations. But what are our current expectations and what does the future hold?
1090. Functional diversity of helper T lymphocytes.
The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses. Defining the cellular and molecular mechanisms of helper-T-cell differentiation should lead to rational strategies for manipulating immune responses for prophylaxis and therapy.
1091. Clonal selection and learning in the antibody system.
Each antibody-producing B cell makes antibodies of unique specificity, reflecting a series of ordered gene rearrangements which must be successfully performed if the cell is to survive. A second selection process occurs during immune responses in which a new antibody repertoire is generated through somatic hypermutation. Here only mutants binding antigen with high affinity survive to become memory cells. Cells expressing autoreactive receptors are counter-selected at both stages. This stringent positive and negative selection allows the generation and diversification of cells while rigorously controlling their specificity.
1092. Molecular chaperones in cellular protein folding.
The folding of many newly synthesized proteins in the cell depends on a set of conserved proteins known as molecular chaperones. These prevent the formation of misfolded protein structures, both under normal conditions and when cells are exposed to stresses such as high temperature. Significant progress has been made in the understanding of the ATP-dependent mechanisms used by the Hsp70 and chaperonin families of molecular chaperones, which can cooperate to assist in folding new polypeptide chains.
1093. The history of the galaxies.
Astronomical observations now reach far enough back in time, in enough depth and detail, to reveal the history of galaxies since their formation. The early Universe contained a network of gas clouds that filled much of the space between the young galaxies, where stars were forming at a high rate. Since then, intergalactic space has been swept clean, and galaxies have continued to convert the dwindling supply of gas slow into stars.
1096. Essential flexibility in the T-cell recognition of antigen.
alpha beta T cells specifically recognize a ligand composed of a peptide bound to a self-major-histocompatibility-complex molecule, but the recognition of slightly altered ligands by T cells can lead to a partial activation. This flexibility is crucial for T-cell development and can have both beneficial and harmful effects on peripheral T cells.
1097. State-dependent life histories.
Life-history theory is concerned with strategic decisions over an organism's lifetime. Evidence is accumulating about the way in which these decisions depend on the organism's physiological state and other components such as external circumstances. Phenotypic plasticity may be interpreted as an organism's response to its state. The quality of offspring may depend on the state and behaviour of the mother. Recent theoretical advances allow these and other state-dependent effects to be modelled within the same framework.
1098. Role of hydration and water structure in biological and colloidal interactions.
The conventional explanation of why hydrophilic surfaces and macromolecules remain well separated in water is that they experience a monotonically repulsive hydration force owing to structuring of water molecules at the surfaces. A consideration of recent experimental and theoretical results suggests an alternative interpretation in which hydration forces are either attractive or oscillatory, and where repulsions have a totally different origin. Further experiments are needed to distinguish between these possibilities.
1099. The enigma of the natural killer cell.
Natural killer (NK) cells are controlled by receptors specific for polymorphic determinants of class I molecules of the major histocompatibility complex (MHC). The contrasting properties of NK and cytotoxic T cell (CTL) class I receptors provide complementarity in the cytolytic lymphocyte response to viruses, tumours and transplants. Whereas human NK cell class I receptors consist of immunoglobulin domains, their mouse counterparts resemble C-type lectins. This difference may reflect the receptors' diverse and rapidly evolving class I ligands.
1100. Plasmid-based transgenic mouse model for studying in vivo mutations.
A new transgenic mouse model for studying in vivo somatic mutations is based on the efficient recovery of chromosomally integrated lacZ-containing plasmids, using magnetic beads.
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