Structure of PTB bound to RNA: specific binding and implications for splicing regulation

The polypyrimidine tract binding protein (PTB) is a 58-kilodalton RNA binding protein involved in multiple aspects of messenger RNA metabolism, including the repression of alternative exons. We have determined the solution structures of the four RNA binding domains (RBDs) of PTB, each bound to a CUCUCU oligonucleotide. Each RBD binds RNA with a different binding specificity. RBD3 and RBD4 interact, resulting in an antiparallel orientation of their bound RNAs. Thus, PTB will induce RNA looping when bound to two separated pyrimidine tracts within the same RNA. This leads to structural models for how PTB functions as an alternative-splicing repressor.     

Protein synthesis: differential stimulation of cell-specific proteins in epithelial cells of chick oviduct

Immunofluorescent and radioautographic studies demonstrate that ovalbumin and avidin are cell-specific proteins synthesized by different epithelial cells in the chick oviduct mucosa. The mechanism of the selective induction of ovalbumin synthesis by estrogen and of avidin synthesis by progesterone may be through stimulation of specific target cells by these hormones.     

The chemistry of sexual deception in an orchid-wasp pollination system

The "sexually deceptive" orchid Chiloglottis trapeziformis attracts males of its pollinator species, the thynnine wasp Neozeleboria cryptoides, by emitting a unique volatile compound, 2-ethyl-5-propylcyclohexan-1,3-dione, which is also produced by female wasps as a male-attracting sex pheromone.     

Pattern-oriented modeling of agent-based complex systems: lessons from ecology

Agent-based complex systems are dynamic networks of many interacting agents; examples include ecosystems, financial markets, and cities. The search for general principles underlying the internal organization of such systems often uses bottom-up simulation models such as cellular automata and agent-based models. No general framework for designing, testing, and analyzing bottom-up models has yet been established, but recent advances in ecological modeling have come together in a general strategy we call pattern-oriented modeling. This strategy provides a unifying framework for decoding the internal organization of agent-based complex systems and may lead toward unifying algorithmic theories of the relation between adaptive behavior and system complexity.     

Inhibition of self-binding antibodies (autobodies) by a VH-derived peptide

The self-binding properties of a dominant idiotypic antibody (T15) and a minor idiotypic antibody (M603), both specific for phosphorylcholine, were examined as models of self-binding antibodies (autobodies). Observed differences in the self-binding affinity of T15 and M603 relate to variable sequence differences in their respective heavy and light chains. A molecular recognition theory based on the translation of coding and noncoding DNA strands was used to identify complementary amino acid sequences responsible for self-binding. The second hypervariable region of the heavy chain domain, extending into the third framework region, was predicted as the primary self-binding locus. Among peptides synthesized with different variable heavy and light chain regions, a 24-residue peptide spanning the second hypervariable and third framework regions of the heavy chain of T15 was nearly as effective as phosphorycholine in inhibiting the self-binding complexes.     

Mutations in dynein link motor neuron degeneration to defects in retrograde transport

Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Although the causative genetic alterations are known for some cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown. Here we show that missense point mutations in the cytoplasmic dynein heavy chain result in progressive motor neuron degeneration in heterozygous mice, and in homozygotes this is accompanied by the formation of Lewy-like inclusion bodies, thus resembling key features of human pathology. These mutations exclusively perturb neuron-specific functions of dynein.     

Effects of basal debris on glacier flow

Glacier movement is resisted partially by debris, either within glaciers or under glaciers in water-saturated layers. In experiments beneath a thick, sliding glacier, ice containing 2 to 11% debris exerted shear traction of 60 to 200 kilopascals on a smooth rock bed, comparable to the total shear traction beneath glaciers and contrary to the usual assumption that debris-bed friction is negligible. Imposed pore-water pressure that was 60 to 100% of the normal stress in a subglacial debris layer reduced shear traction on the debris sufficiently to halt its deformation and cause slip of ice over the debris. Slip resistance was thus less than debris shearing resistance.     

Thymine dimerization in DNA is an ultrafast photoreaction

Femtosecond time-resolved infrared spectroscopy was used to study the formation of cyclobutane dimers in the all-thymine oligodeoxynucleotide (dT)18 by ultraviolet light at 272 nanometers. The appearance of marker bands in the time-resolved spectra indicates that the dimers are fully formed approximately 1 picosecond after ultraviolet excitation. The ultrafast appearance of this mutagenic photolesion points to an excited-state reaction that is approximately barrierless for bases that are properly oriented at the instant of light absorption. The low quantum yield of this photoreaction is proposed to result from infrequent conformational states in the unexcited polymer, revealing a strong link between conformation before light absorption and photodamage.