Intercellular communication in the rat anterior pituitary gland: an in vivo and in vitro study

The concept of "stimulus-secretion coupling" suggested by Douglas and co-workers to explain the events related to monamine discharge by the adrenal medulla (5, 7) may be applied to other endocrine tissues, such as adrenal cortex (36), pancreatic islets (4), and magnocellular hypothalamic neurons (6), which exhibit a similar ion-dependent process of hormone elaboration. In addition, they share another feature, that of joining neighbor cells via membrane junctions (12, 26, and Fletcher, unpublished observation). Given this, and the reports that hormone secretion by the pars distalis also involves a secretagogue-induced decrease in membrane bioelectric potential accompanied by a rise in cellular [Ca++] (27, 34, 41), it was appropriate to test the possibility that cells of the anterior pituitary gland are united by junctions.     

High Altitude Bird Migration at Temperate Latitudes: A Synoptic Perspective on Wind Assistance

At temperate latitudes the synoptic patterns of bird migration are strongly structured by the presence of cyclones and anticyclones, both in the horizontal and altitudinal dimensions. In certain synoptic conditions, birds may efficiently cross regions with opposing surface wind by choosing a higher flight altitude with more favourable wind. We observed migratory passerines at mid-latitudes that selected high altitude wind optima on particular nights, leading to the formation of structured migration layers at varying altitude up to 3 km. Using long-term vertical profiling of bird migration by C-band Doppler radar in the Netherlands, we find that such migration layers occur nearly exclusively during spring migration in the presence of a high-pressure system. A conceptual analytic framework providing insight into the synoptic patterns of wind assistance for migrants that includes the altitudinal dimension has so far been lacking. We present a simple model for a baroclinic atmosphere that relates vertical profiles of wind assistance to the pressure and temperature patterns occurring at temperate latitudes. We show how the magnitude and direction of the large scale horizontal temperature gradient affects the relative gain in wind assistance that migrants obtain through ascending. Temperature gradients typical for northerly high-pressure systems in spring are shown to cause high altitude wind optima in the easterly sectors of anticyclones, thereby explaining the frequent observations of high altitude migration in these synoptic conditions. Given the recurring synoptic arrangements of pressure systems across temperate continents, the opportunities for exploiting high altitude wind will differ between flyways, for example between easterly and westerly oceanic coasts.     

The nature of plant adaptations to salinity stress has trophic consequences

In different ecosystems herbivores highly prefer particular plant species. This is often explained in a stoichiometric framework of nutrient‐based plant adaptations to herbivory. We hypothesize that such super‐palatability can also arise as an evolutionary by‐product of osmoregulatory adaptations of plants to stressful environmental conditions, as salinity, drought and cold. Here, we investigate in a coastal salt marsh why some plant species are highly preferred by migratory brent geese Branta bernicla bernicla in spring while others are avoided. This salt marsh is an important spring staging site for the geese. Sufficient energy storage in a short period is critical to enable their northward migration to Siberia and subsequent reproduction. We test if geese prefer plants that balance their internal osmotic potential with the saline environment through energy‐rich soluble sugars over plant species that use (compartmentalized) salts for this. We find that plant nitrogen and acid detergent fiber content, classic predictors of herbivore preferences, poorly explain which plants the geese prefer. Instead, plant species that are highly preferred by the geese adapt to salinity by high soluble sugar concentrations while avoided species do this by high plant salt concentrations. Thus, the type of osmoregulatory adaptation to stress displayed by different plant species is a good predictor for the food preference of geese on this salt marsh. We suggest that variation in other types of osmoregulation‐based stress adaptations, as plant cold adaptations in tundras and plant drought adaptations in savannas, have similar important consequences for trophic interactions.     

Classification and nomenclature of all human homeobox genes

Background

The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described.

Results

We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive DUX1 to DUX5 homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.

Conclusion

We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.     

Characterization of terminal NeuNAcalpha2-3Galbeta1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis

Group B and C Neisseria meningitidis are the major cause of meningococcal disease in the United States and in Europe. N . meningitidis lipooligosaccharide (LOS), a major surface antigen, can be divided into 12 immunotypes of which L1 through L8 were found among Group B and C organisms. Groups B and C but not Group A may sialylate their LOSs with N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they synthesize CMP-NeuNAc. Using sialic acid-galactose binding lectins as probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4, L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis leukoagglutinin (MAL), which recognizes NeuNAcalpha2- 3Galbeta1-4GlcNAc/Glc sequence, but not to Sambucus nigra agglutinin, which binds NeuNAcalpha2-6Gal sequence. The combination of SDS-PAGE and MAL-blot analyses revealed that these six LOSs contained only the NeuNAcalpha2-3Galbeta1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS components, which have a common terminal lacto-N-neotetraose (LNnT, Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) structure when nonsialylated as shown by previous studies. The LOS-lectin binding was abolished when the LOSs were treated with Newcastle disease viral neuraminidase which cleaves alpha2-->3 linked sialic acid. Methylation analysis of a representative LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thus, these LOSs structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide) and sialylparagloboside and some glycoproteins in having LNnT and N-acetyllactosamine sequences, respectively, with or without alpha2-->3 linked NeuNAc. The molecular mimicry of the LOSs may play a role in the pathogenesis of N.meningitidis by assisting the organism to evade host immune defenses in man.      

Birds flee en mass from New Year's Eve fireworks

Anthropogenic disturbances of wildlife, such as noise, human presence, hunting activity, and motor vehicles, are becoming an increasing concern in conservation biology. Fireworks are an important part of celebrations worldwide, and although humans often find fireworks spectacular, fireworks are probably perceived quite differently by wild animals. Behavioral responses to fireworks are difficult to study at night, and little is known about the negative effects fireworks may have on wildlife. Every year, thousands of tons of fireworks are lit by civilians on New Year's Eve in the Netherlands. Using an operational weather radar, we quantified the reaction of birds to fireworks in 3 consecutive years. Thousands of birds took flight shortly after midnight, with high aerial movements lasting at least 45 min and peak densities measured at 500 m altitude. The highest densities were observed over grasslands and wetlands, including nature conservation sites, where thousands of waterfowl rest and feed. The Netherlands is the most important winter staging area for several species of waterfowl in Europe. We estimate that hundreds of thousands of birds in the Netherlands take flight due to fireworks. The spatial and temporal extent of disturbance is substantial, and potential consequences are discussed. Weather radar provides a unique opportunity to study the reaction of birds to fireworks, which has otherwise remained elusive.     

Requirements for effective antitumor responses of TCR transduced T cells

Adoptive transfer of TCR gene-modified T cells has been proposed as an attractive approach to target tumors for which it is difficult or impossible to induce strong tumor-specific T cell responses by vaccination. Whereas the feasibility of generating tumor Ag-specific T cells by gene transfer has been demonstrated, the factors that determine the in vivo effectiveness of TCR-modified T cells are largely unknown. We have analyzed the value of a number of clinically feasible strategies to enhance the antitumor potential of TCR modified T cells. These experiments reveal three factors that contribute greatly to the in vivo potency of TCR-modified T cells. First, irradiation-induced host conditioning is superior to vaccine-induced activation of genetically modified T cells. Second, increasing TCR expression through genetic optimization of TCR sequences has a profound effect on in vivo antitumor activity. Third, a high precursor frequency of TCR modified T cells within the graft is essential. Tumors that ultimately progress in animals treated with this optimized regimen for TCR-based adoptive cell transfer invariably display a reduced expression of the target Ag. This suggests TCR gene therapy can achieve a sufficiently strong selective pressure to warrant the simultaneous targeting of multiple Ags. The strategies outlined in this study should be of value to enhance the antitumor activity of TCR-modified T cells in clinical trials.     

Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure

Background  

Efficient communication between distant sites within a protein is essential for cooperative biological response. Although often associated with large allosteric movements, more subtle changes in protein dynamics can also induce long-range correlations. However, an appropriate formalism that directly relates protein structural dynamics to information exchange between functional sites is still lacking.