The specific antigen-binding cell populations of individual fetal mouse spleens: repertoire composition, size, and genetic control

In order to analyze the genetic and physiological basis of controls affecting the generation of the repertoire of antigen-binding cells in fetal mice, we have measured the numbers of spleen cells specific for each of four antigens as a function of the total numbers of nucleated and Ig-bearing cells in inbred, hybrid, and random bred fetuses. For each of the two inbred strains BALB/c and CBA/J, the proportion of nucleated cells specific for a given antigen was the same for all individuals of the strain at the 18th day of gestation. The proportion did vary from antigen to antigen, however, and for each antigen the proportion of specific cells observed in CBA/J fetuses was approximately four times that observed in BALB/c fetuses. This difference appeared to be due to a difference between the two strains in the relative size of the repertoire of antigen-binding spleen cells at this stage of development, inasmuch as the frequency of Ig-bearing spleen cells in CBA/J fetuses was likewise approximately four times that observed in BALB/c fetuses. In random bred Swiss-L fetal mice at the 18th day of gestation, the proportion of cells specific for a given antigen varied significantly from one individual to the next. The ratio of proportions of the two antigens observed was constant from individual to individual, however, and this constant ratio differed significantly from the ratio observed for the same two antigens in fetal BALB/c and CBA/J inbred mice. These data suggest that the ontogeny of the repertoire of antigen-binding cells in fetal mice is subject to at least two independent sets of controls, one affecting the relative size of the repertoire in the spleen, and the other affecting the distribution of antigen-binding specificities within that repertoire. Analysis of repertoire size and composition in the spleens of hybrid fetuses confirmed the observation that the two parameters are controlled independently, and suggested further that the control of repertoire size in these fetuses is due to the action of one or a few closely-linked autosomal Mendelian genes. These data are consistent with models for the origin of antibody diversity in which the genes coding for the full repertoire of antibodies are generated somatically from a small number of germ-line genes early in development and in the absence of any strong positive or negative selection with respect to antigenic specificity

Universality in Systems with Power-Law Memory and Fractional Dynamics

There are a few different ways to extend regular nonlinear dynamical systems by introducing power-law memory or considering fractional differential/difference equations instead of integer ones. This extension allows the introduction of families of nonlinear dynamical systems converging to regular systems in the case of an integer power-law memory or an integer order of derivatives/differences. The examples considered in this review include the logistic family of maps (converging in the case of the first order difference to the regular logistic map), the universal family of maps, and the standard family of maps (the latter two converging, in the case of the second difference, to the regular universal and standard maps). Correspondingly, the phenomenon of transition to chaos through a period doubling cascade of bifurcations in regular nonlinear systems, known as "universality", can be extended to fractional maps, which are maps with power-/asymptotically power-law memory. The new features of universality, including cascades of bifurcations on single trajectories, which appear in fractional (with memory) nonlinear dynamical systems are the main subject of this review.Comment: 23 pages 7 Figures, to appear Oct 28 201

Targeted ablation and reorganization of the principal preplate neurons and their neuroblasts identified by golli promoter transgene expression in the neocortex of mice

The present study delineates the cellular responses of dorsal pallium to targeted genetic ablation of the principal preplate neurons of the neocortex. Ganciclovir treatment during prenatal development (E11–E13; where E is embryonic day) of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene, linked to HSV-TK (herpes simplex virus-thymidine kinase), τ-eGFP (τ-enhanced green fluorescent protein) and lacZ (lacZ galactosidase) reporters] localized in preplate neurons. Morphogenetic fates of attacked neurons and neuroblasts, and their successors, were assessed by multiple labelling in time-series comparisons between ablated (HSV-TK+/0) and control (HSV-TK0/0) littermates. During ablation generation, neocortical growth was suppressed, and compensatory reorganization of non-GPT ventricular zone progenitors of dorsal pallium produced replacements for killed GPT neuroblasts. Replacement and surviving GPT neuroblasts then produced replacements for killed GPT neurons. Near-normal restoration of their complement delayed the settlement of GPT neurons into the reconstituted preplate, which curtailed the outgrowth of pioneer corticofugal axons. Based on this evidence, we conclude that specific cell killing in ablated mice can eliminate a major fraction of GPT neurons, with insignificant bystander killing. Also, replacement GPT neurons in ablated mice originate exclusively by proliferation from intermediate progenitor GPT neuroblasts, whose complement is maintained by non-GPT progenitors for inductive regulation of the total complement of GPT neurons. Finally, GPT neurons in both normal and ablated mice meet all morphogenetic criteria, including the ‘outside-in’ vertical gradient of settlement, presently used to identify principal preplate neurons. In ablated mice, delayed organization of these neurons desynchronizes and isolates developing neocortex from the rest of the brain, and permanently impairs its connectivity

Fractional Zaslavsky and Henon Discrete Maps

This paper is devoted to the memory of Professor George M. Zaslavsky passed away on November 25, 2008. In the field of discrete maps, George M. Zaslavsky introduced a dissipative standard map which is called now the Zaslavsky map. G. Zaslavsky initialized many fundamental concepts and ideas in the fractional dynamics and kinetics. In this paper, starting from kicked damped equations with derivatives of non-integer orders we derive a fractional generalization of discrete maps. These fractional maps are generalizations of the Zaslavsky map and the Henon map. The main property of the fractional differential equations and the correspondent fractional maps is a long-term memory and dissipation. The memory is realized by the fact that their present state evolution depends on all past states with special forms of weights.Comment: 26 pages, LaTe

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

Demographic, Psychological, and Social Characteristics of Self-Identified Lesbian, Gay, and Bisexual Adults in a US Probability Sample

Using data from a US national probability sample of self-identified lesbian, gay, and bisexual adults (N = 662), this article reports population parameter estimates for a variety of demographic, psychological, and social variables. Special emphasis is given to information with relevance to public policy and law. Compared with the US adult population, respondents were younger, more highly educated, and less likely to be non-Hispanic White, but differences were observed between gender and sexual orientation groups on all of these variables. Overall, respondents tended to be politically liberal, not highly religious, and supportive of marriage equality for same-sex couples. Women were more likely than men to be in a committed relationship. Virtually all coupled gay men and lesbians had a same-sex partner, whereas the vast majority of coupled bisexuals were in a heterosexual relationship. Compared with bisexuals, gay men and lesbians reported stronger commitment to a sexual-minority identity, greater community identification and involvement, and more extensive disclosure of their sexual orientation to others. Most respondents reported experiencing little or no choice about their sexual orientation. The importance of distinguishing among lesbians, gay men, bisexual women, and bisexual men in behavioral and social research is discussed

Functional significance of the hepaCAM gene in bladder cancer

<p>Abstract</p> <p>Background</p> <p>The hepaCAM gene encodes a new immunoglobulin-like cell adhesion molecule, and its expression is suppressed in a variety of human cancers. Additionally, hepaCAM possesses properties often observed in tumor suppressor genes. However, the expression and biological function of hepaCAM has not been investigated in bladder cancer. Therefore we sought to examine hepaCAM expression and the relationship between its structure and function in human transitional cell carcinoma of bladder (TCCB).</p> <p>Materials and methods</p> <p>HepaCAM expression was evaluated in 28 normal and 34 TCCB bladder specimens and 2 TCCB cell lines using semi-quantitative RT-PCR. The wild-type hepaCAM and the extracellular domain-truncated mutant gene were transfected into the TCCB cell line T24, and the biological properties of both the wild-type gene and the domain-truncated mutant were then assessed.</p> <p>Results</p> <p>HepaCAM expression was down-regulated in 82% (28/34) of TCCB specimens and undetectable in the 2 TCCB cell lines tested. The localization of hepaCAM appeared to be dependent on cell density in T24 cells. In widely spread cells, hepaCAM accumulated on the perinuclear membrane and the cell surface protrusions, whereas in confluent cells, hepaCAM was predominantly localized at the sites of cell-cell contacts on the cell membrane. Functionally, hepaCAM expressed not only increased cell spreading, delayed cell detachment, enhanced wound healing and increased cell invasion; it also inhibited cell growth (P < 0.01). When the extracellular domain was deleted, the localization of hepaCAM was significantly altered, and it lost both its adhesive function and its influence on cell growth.</p> <p>Conclusions</p> <p>HepaCAM is involved in cell adhesion and growth control, and its expression is frequently silenced in TCCB. The extracellular domain of hepaCAM is essential to its physiological and biological functions.</p

Degeneracy: a link between evolvability, robustness and complexity in biological systems

A full accounting of biological robustness remains elusive; both in terms of the mechanisms by which robustness is achieved and the forces that have caused robustness to grow over evolutionary time. Although its importance to topics such as ecosystem services and resilience is well recognized, the broader relationship between robustness and evolution is only starting to be fully appreciated. A renewed interest in this relationship has been prompted by evidence that mutational robustness can play a positive role in the discovery of adaptive innovations (evolvability) and evidence of an intimate relationship between robustness and complexity in biology. This paper offers a new perspective on the mechanics of evolution and the origins of complexity, robustness, and evolvability. Here we explore the hypothesis that degeneracy, a partial overlap in the functioning of multi-functional components, plays a central role in the evolution and robustness of complex forms. In support of this hypothesis, we present evidence that degeneracy is a fundamental source of robustness, it is intimately tied to multi-scaled complexity, and it establishes conditions that are necessary for system evolvability