Loss of antibody production accompanied by chromosome loss in a cloned hybrid line secreting antibodies to sheep red blood cells

Summary Somatic cell hybrids between Sp2/O-Ag14 mouse myeloma cells and lymphocytes derived from BALB/c mice hyperimmunized with sheep red blood cells (SRBC) were produced. One hybrid producing IgG₁ antibody to SRBC was selected, cloned twice and subsequently transferred to BALB/c mice. After a number of transfers it was found that the antibody titer in ascitec fluid gradually decreased. Cytogenetic analysis revealed gradual chromosome loss in the hybrid clone, which produced progressively less antibody.     

Emergence of cooperation and evolutionary stability in finite populations

To explain the evolution of cooperation by natural selection has been a major goal of biologists since Darwin. Cooperators help others at a cost to themselves, while defectors receive the benefits of altruism without providing any help in return. The standard game dynamical formulation is the 'Prisoner's Dilemma', in which two players have a choice between cooperation and defection. In the repeated game, cooperators using direct reciprocity cannot be exploited by defectors, but it is unclear how such cooperators can arise in the first place. In general, defectors are stable against invasion by cooperators. This understanding is based on traditional concepts of evolutionary stability and dynamics in infinite populations. Here we study evolutionary game dynamics in finite populations. We show that a single cooperator using a strategy like 'tit-for-tat' can invade a population of defectors with a probability that corresponds to a net selective advantage. We specify the conditions required for natural selection to favour the emergence of cooperation and define evolutionary stability in finite populations.     

Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles

Protein-based hydrogels are used for many applications, ranging from food and cosmetic thickeners to support matrices for drug delivery and tissue replacement. These materials are usually prepared using proteins extracted from natural sources, which can give rise to inconsistent properties unsuitable for medical applications. Recent developments have utilized recombinant DNA methods to prepare artificial protein hydrogels with specific association mechanisms and responsiveness to various stimuli. Here we synthesize diblock copolypeptide amphiphiles containing charged and hydrophobic segments. Dilute solutions of these copolypeptides would be expected to form micelles; instead, they form hydrogels that retain their mechanical strength up to temperatures of about 90 degrees C and recover rapidly after stress. The use of synthetic materials permits adjustment of copolymer chain length and composition, which we varied to study their effect on hydrogel formation and properties. We find that gelation depends not only on the amphiphilic nature of the polypeptides, but also on chain conformations--alpha-helix, beta-strand or random coil. Indeed, shape-specific supramolecular assembly is integral to the gelation process, and provides a new class of peptide-based hydrogels with potential for applications in biotechnology.     

Antibody neutralization and escape by HIV-1

Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.     

A gene expression atlas of the central nervous system based on bacterial artificial chromosomes

The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.     

The evolution of syntactic communication

Animal communication is typically non-syntactic, which means that signals refer to whole situations. Human language is syntactic, and signals consist of discrete components that have their own meanings. Syntax is a prerequisite for taking advantage of combinatorics, that is, "making infinite use of finite means. The vast expressive power of human language would be impossible without syntax, and the transition from non-syntactic to syntactic communication was an essential step in the evolution of human language. We aim to understand the evolutionary dynamics of this transition and to analyse how natural selection can guide it. Here we present a model for the population dynamics of language evolution, define the basic reproductive ratio of words and calculate the maximum size of a lexicon. Syntax allows larger repertoires and the possibility to formulate messages that have not been learned beforehand. Nevertheless, according to our model natural selection can only favour the emergence of syntax if the number of required signals exceeds a threshold value. This result might explain why only humans evolved syntactic communication and hence complex language.     

Differential responses to nitrogen form and concentration for Oryzopsis hymenoides and Elymus lanceolatus

In a greenhouse experiment, effects of nitrogen form and concentration on productivity and dry matter allocation differed between two species native to semiarid ecosystems of the Great Basin. Aboveground production of green surface area and of dry matter were consistently enhanced by increased nitrogen for the rhizomatous grass Elymus lanceolatus , but not for the bunchgrass Oryzopsis hymenoides . These differences were likely due to inherently low growth rates of O. hymenoides . Aboveground dry matter allocation also differed between the two species. O. hymenoides had more leaves per tiller with increased nitrogen, whereas leaf size but not number increased for E. lanceolatus . Furthermore, increases in tiller density with increased nitrogen for E. lanceolatus were almost three times greater than those for O. hymenoides . E. lanceolatus , but not O. hymenoides , was sensitive to the form of nitrogen supplied to the plants. When NH 4 -N was the only form of nitrogen supplied, high concentrations of NH 4 -N inhibited aboveground production of E. lanceolatus .