Free Edges in Epithelial Cell Sheets Stimulate Epidermal Growth Factor Receptor Signaling

The ability of epithelia to migrate and cover wounds is essential to maintaining their functions as physical barriers. Wounding induces many cues that may affect the transition to motility, including the immediate mechanical perturbation, release of material from broken cells, new interactions with adjacent extracellular matrix, and breakdown of physical separation of ligands from their receptors. Depending on the exact nature of wounds, some cues may be present only transiently or insignificantly. In many epithelia, activation of the epidermal growth factor receptor (EGFR) is a central event in induction of motility, and we find that its continuous activation is required for progression of healing of wounds in sheets of corneal epithelial cells. Here, we examine the hypothesis that edges, which are universally and continuously present in wounds, are a cue. Using a novel culture model we find that their presence is sufficient to cause activation of the EGFR and increased motility of cells in the absence of other cues. Edges that are bordered by agarose do not induce activation of the EGFR, indicating that activation is not due to loss of any specific type of cell–cell interaction but rather due to loss of physical constraints.     

Relative regeneration proficiency ofArabidopsis thaliana ecotypes

We have compared regeneration proficiency for cultured explants from different tissues of different ecotypes ofArabidopsis thaliana. Proficiency varies widely with both tissue and ecotype, and is highest when the flux of light during regeneration is low. Analysis of F1 hybrids suggests that high proficiency is dominant to low proficiency.     

Two-phase species–time relationships in North American land birds

The species–time relationship (STR) is a macroecological pattern describing the increase in the observed species richness with the length of time censused. Understanding STRs is important for understanding the ecological processes underlying temporal turnover and species richness. However, accurate characterization of the STR has been hampered by the influence of sampling. I analysed STRs for 521 breeding bird survey communities. I used a model of sampling effects to demonstrate that the increase in richness was not due exclusively to sampling. I estimated the time scale at which ecological processes became dominant over sampling effects using a two‐phase model combining a sampling phase and either a power function or logarithmic ecological phase. These two‐phase models performed significantly better than sampling alone and better than simple power and logarithmic functions. Most community dynamics were dominated by ecological processes over scales <5 years. This technique provides an example of a rigorous, quantitative approach to separating sampling from ecological processes.     

Selenium and cellular immunity

Selenium deficiency can lead to impaired immune function and reduced T-cell counts, as well as various specific disorders. Significantly, in ARC and AIDS patients, a progressive decline in plasma Se, paralleling T-cell loss, has been widely documented. Since evidence now suggests that there is an extremely high turnover of CD4+ T-cells in AIDS patients, with billions of new cells lost and replaced daily, any exceptional requirement for Se in lymphocytes could contribute to this progressive Se depletion. Thus, it may be significant that, over-lapping the known genes in the +1 reading frame, the mRNAs of several T-cell associated genes (CD4, CD8, HLA-DR p33) have open reading frames (ORFs) with as many as 10 in-frame UGA codons (CD4, p33), a clustering that is highly improbable by chance alone, and reminiscent of selenoprotein P, the predominant plasma form of Se. The presence of these ORFs, along with potential stem-loop RNA structures displaying consensus selenocysteine insertion sequences, AUG(N)_mAAA(N)_nUGR, suggests that these mRNAs may encode selenoproteins, in addition to the known T-cell glycoproteins. If so, the roles of Se in the immune system may be more diverse than previously suspected.     

Transcapillary escape rate of albumin in humans during exercise-induced hypervolemia

Haskell, Andrew, Ethan R. Nadel, Nina S. Stachenfeld, KeiNagashima, and Gary W. Mack. Transcapillary escape rate of albuminin humans during exercise-induced hypervolemia. J. Appl. Physiol. 83(2): 407-413, 1997.To test thehypotheses that plasma volume (PV) expansion 24 h after intenseexercise is associated with reduced transcapillary escape rate ofalbumin (TER_alb) and that localchanges in transcapillary forces in the previously active tissues favorretention of protein in the vascular space, we measured PV,TER_alb, plasma colloid osmoticpressure (COP_p), interstitialfluid hydrostatic pressure (Pi), and colloid osmotic pressure in legmuscle and skin and capillary filtration coefficient (CFC) in the armand leg in seven men and women before and 24 h after intense uprightcycle ergometer exercise. Exercise expanded PV by 6.4% at 24 h (43.9 ± 0.8 to 46.8 ± 1.2 ml/kg, P < 0.05) and decreased total protein concentration (6.5 ± 0.1 to6.3 ± 0.1 g/dl, P < 0.05) andCOP_p (26.1 ± 0.8 to 24.3 ± 0.9 mmHg, P < 0.05), although plasmaalbumin concentration was unchanged. TER_alb tended to decline (8.4 ± 0.5 to 6.5 ± 0.7%/h, P = 0.11) and was correlated with the increase in PV(r = 0.69,P < 0.05). CFC increased in the leg(3.2 ± 0.2 to 4.3 ± 0.5 µl · 100 g¹ · min¹ · mmHg¹,P < 0.05), and Pi showed a trend toincrease in the leg muscle (2.8 ± 0.7 to 3.8 ± 0.3 mmHg, P = 0.08). These datademonstrate that TER_alb isassociated with PV regulation and that local transcapillary forcesin the leg muscle may favor retention of albumin in the vascular spaceafter exercise.

     

Sublocalization of an Ataxia-Telangiectasia Gene Distal to D11S384 by Ancestral Haplotyping In Costa Rican Families

In an effort to localize a gene for ataxia-telangiectasia (A-T), we have genotyped 27 affected Costa Rican families, with 13 markers, in the chromosome 11q22-23 region. Significant linkage disequilibrium was detected for 9/13 markers between D11S1816 and D11S1391. Recombination events observed in these pedigrees places A-T between D11S1819 and D11S1960. One ancestral haplotype is common to 24/54 affected chromosomes and roughly two-thirds of the families. Inferred (ancestral) recombination events involving this common haplotype in earlier generations suggest that A-T is distal to D11S384 and proximal to D11S1960. Several other common haplotypes were identified, consistent with multiple mutations in a single gene. When considered together with all other evidence, this study further sublocalizes the major A-T locus to ≈200 kb, between markers S384 and S535.     

T lymphocytes responding to Mls-locus antigens are Lyt-1+, 2− andI-A restricted

We have investigated primary and secondary responses of mouse splenic T cells to strong mixed lymphocyte stimulating antigens controlled by theMls locus using MHC-identical mixtures of cells. Our studies show that strong primaryMls-locus specific responses involve recognition of self I-A antigens, since BUdR and light suicide or F1 into parent radiation bone-marrow chimeras both demonstrate a preference of unprimed F1 T cells to respond to Mis-locus antigens associated with one parent's MHC antigens. Furthermore, conventional anti-I-A antisera and monoclonal anti-I-A antibody both inhibitMls-locus responses in an MHC-specific manner. Finally, as is typical of T cells responding to I-A antigens or to nominal antigens associated with self I-A,Mlslocus responses are mediated by Lyt-1⁺, 2^– cells. One striking finding in these studies was the very high frequency of cells capable of responding to Mls-locus antigens, the highest being 1/300 splenic T cells. This plus evidence for recruitment during primaryMls-locus responses may account for reports of a lack ofI-A restriction in secondary anti-Mls locus responses to strong Mls-locus antigens, a finding with which we concur. The possibility that these secondary responses between noncongenic strains of mice may be directed at other genetic loci is also discussed. These experiments leave open the question of the biological role of theMls-locus and of the very large number of T cells reactive to it.Abbreviations used in this paper MHC Major histocompatibility complex - MIg Mouse immunoglobulin - MLC Mixed lymphocyte culture - TCGF T-cell growth factor     

Domination or equilibrium

In the dynamics of an evolutionary game an equilibrium in which all strategy types occur is called an interior equilibrium. Interior equilibria fail to exist only when there is domination among the strategy types.     

Linkage of the gene controlling the synthesis of the fourth component of complement to the major histocompatibility complex of the guinea pig

C4-deficient (C4D) guinea pigs are lacking in C4 synthesis, a condition that appears to be caused by a structural gene defect. This defect is inherited as a simple autosomal recessive trait. We have demonstrated linkage between C4D and the major histocompatibility complex of the guinea pig (GPLA). Inbred C4D and inbred strain 13 guinea pigs appear to have the same GPLA haplotype. The use of these two strains should provide an animal model for reconstitution studies of C4 synthesis and for studied exploring the possible role of C4 in cellular and humoral immune responses.Abbreviations used in this paper are C4D deficiency of the fourth component of complement - MHC major histocompatibility complex - GPLA major histocompatibility complex of the guinea pig - MLC mixed lymphocyte culture     

Panmixia across elevation in thermally sensitive Andean dung beetles

Janzen's seasonality hypothesis predicts that organisms inhabiting environments with limited climatic variability will evolve a reduced thermal tolerance breadth compared with organisms experiencing greater climatic variability. In turn, narrow tolerance breadth may select against dispersal across strong temperature gradients, such as those found across elevation. This can result in narrow elevational ranges and generate a pattern of isolation by environment or neutral genetic differentiation correlated with environmental variables that are independent of geographic distance. We tested for signatures of isolation by environment across elevation using genome‐wide SNP data from five species of Andean dung beetles (subfamily Scarabaeinae) with well‐characterized, narrow thermal physiologies, and narrow elevational distributions. Contrary to our expectations, we found no evidence of population genetic structure associated with elevation and little signal of isolation by environment. Further, elevational ranges for four of five species appear to be at equilibrium and show no decay of genetic diversity at range limits. Taken together, these results suggest physiological constraints on dispersal may primarily operate outside of a stable realized niche and point to a lower bound on the spatial scale of local adaptation.