Syntheses and structure–activity relationships for some triazolyl p38α MAPK inhibitors

The design, synthesis and biological evaluation of novel triazolyl p38α MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups were introduced via a ‘click’ reaction of functional azides with 2-alkynyl imidazoles and isosteric oxazoles to generate two small libraries of 1,4-disubstituted 1,2,3-triazolyl p38α MAPK inhibitors. Triazoles with low IC₅₀ values and desired physicochemical properties were screened for in vitro downregulation of proinflammatory gene expression and were formulated in SAINT-O-Somes. Triazolyl p38α MAPK inhibitor 88 (IC₅₀ = 0.096 μM) displayed the most promising in vitro activity.     

Epilogue — Demography and anthropology

As a conclusion, this paper reviews briefly the content of the volume. The wealth of demographic data has not been adequately exploited in anthropology; this is why this publication is valuable in showing attempts to apply demographic data in a variety of anthropological problems. This symposium has explored many interesting points which we recall here. Yet it has also opened up a whole range of further questions on the material presented as well as in this broad field. Several directions of research could be developed, for instance, testing among human populations, over long periods, the ecological thoughts of ecosystems evolving as a cascade of instabilities, rather than a succession of equilibrium states. Let us also recall the pervasive nature of demographic facts in topics such as the energy cycle or the genetic structure and evolution of human populations.     

A three-step screening procedure to identify the mode of phloem loading in intact leaves

A three-step screening method was developed to identify the mode of phloem loading in intact leaves. Phloem loading of ¹⁴CO₂-derived photosynthate was challenged by p-chloromercuribenzenesulfonic acid (PCMBS) in leaves of dicotyledons with either a symplasmic (type 1, with intermediary cells as companion cells) or apoplasmic (type 2b, with transfer cells as companion cells) minor-vein configuration. Firstly, photosynthate export as the result of phloem loading was measured by collection of phloem exudate from the petiole. The PCMBS had virtually no effect on photosynthate export in representatives of type-1 families (Lamiaceae, Lythraceae, Onagraceae, Saxifragaceae). In contrast, photosynthate export was strongly reduced by PCMBS in representatives of type-2b families (Asteraceae, Balsaminaceae, Dipsacaceae, Linaceae, Tropaeolaceae, Valerianaceae) and type-2b members of polytypical families (Fabaceae, Scrophulariaceae). Secondly, densitometric measurements of leaf autoradiographs demonstrated that the contrast between the mesophyll and the lower-order veins was hardly affected by PCMBS treatment in type-1 species, whereas PCMBS strongly reduced the contrast in type-2b species. Thirdly, separate ¹⁴C-radioassays of vein and mesophyll tissues confirmed this observation. The three-step procedure thus revealed a strong and consistent reduction of phloem loading by PCMBS in type-2b species which was absent in type-1 species. In conclusion, phloem loading in type-2b species occurs via the apoplast and type-1 species execute an alternative — most likely symplasmic — mode of phloem loading.Abbreviations PCMBS p-chloromercuribenzenesulfonic acid - SE/CC-complex sieve element/companion cell complex We gratefully acknowledge the expert help of Dr. Maarten Terlou, Department of Image Processing and Design, University of Utrecht, in carrying out the densitometric measurements.     

The Cytological Recognition of African Siderosis On Bone Smears

Eight cases of African siderosis primarily recognized on cytological smears are presented and discussed. All the smears were obtained from Jamshidi needle biopsies of vertebral bodies. Six cases showed siderosis only, while a seventh showed two pathological processes on one slide, namely metastatic keratinizing squamous carcinoma and siderosis. The remaining case showed cytological evidence of tuberculosis and siderosis. All cases were histologically confirmed, an additional feature in two cases being osseous tuberculosis which was not evident on the cytological smears. A search of the literature failed to reveal any report on the cytological recognition of this disease, or its association with tuberculosis.     

Dynamic features of cells expressing macrophage properties in tissue cultures of dissociated cerebral cortex from the rat

Summary Two previously identified forms of macrophage were investigated in primary cultures of cerebral cortical cells. Dynamic features were revealed through time-lapse video recording and aspects of macrophage function were assessed. The two cell forms were shown to be different pre-mitotic stages of a single cell type. The cell cycle for these cells involved an initial large, flat, quiescent cell which retracted to yield a slightly rounded form with numerous processes. This latter form lost processes and developed profuse filopodia as it became very rounded just prior to division; both resulting daughter cells then regained the initial large flat appearance. These cells possessed several properties of macrophages, including phagocytosis, nucleoside diphosphatase enzyme, and CR3 receptors. These properties were transient, expressed just before and after mitosis, but subsequently down-regulated in the flat daughter cells. Because of this feature, it was difficult to determine the exact size of this cell population; however, the observed rate of proliferation suggests it may be substantial. It is suggested that these cells correspond to non-microglial macrophages of brain tissue and, because of their significant down-regulation, they may be difficult to detect. This may be important in studies of brain accessory immune cells in tissue culture.     

Studies of the proliferation and differentiation of immature myeloid cells in vitro: 4: Preculture proto-oncogene expression and the behaviour of myeloid leukemia cells in vitro

Studies were conducted to determine the relationship between the pretherapy characteristics of leukemia cells and their behaviour during culture in vitro. Leukemia cells which proliferated well in vitro also proliferated well in vivo. Cells which manifested myeloid or monocytic differentiation in vivo tended to manifest differentiation along these lines in vitro. Cells which manifested high levels of expression of c-fms, c-fes, or triose phosphate isomerase prior to culture were likely to differentiate in vitro, with high levels of c-fes expression being related to myeloid maturation. These observations suggest that differentiation at the molecular level prior to culture is a requisite for leukemia cell differentiation in vitro. The same may be true for differentiation in vivo under the influence of exogenously administered agents such as cytotoxic chemotherapy or recombinant growth factors.     

Evidences for genetic differentiation within the highly endemic and endangered annual fish Austrolebias nigrofasciatus (Cyprinodontiformes: Rivulidae)

Samples of Austrolebias nigrofasciatus (n = 103), an endangered species of annual fish endemic to a small area of the Patos-Mirim lagoon system encompassing the São Gonçalo Channel lowlands, were collected from eight isolated temporary ponds, four located at the known distribution range of the species and four located along the Piratini River lowlands, where morphologically different individuals were found. In the laboratory, fragments of the mitochondrial cytochrome c oxidase I (coI), cytochrome b (cytb) and nuclear rhodopsin (rho) genes were amplified, purified and sequenced for 100, 99 and 58 of these individuals, respectively. Samples were further analysed using phylogenetic and phylogeographic methods to evaluate the patterns of genetic diversity and differentiation presented within and between populations, while assessing their evolutionary history, in order to guide the application of further conservation strategies. We found that the four new populations from the Piratini River lowlands encompass a different lineage of A. nigrofasciatus that diverged from that encountered in the São Gonçalo Channel at approximately 0.165 M years before present, during a population expansion and did not yet attain reciprocal monophyly. This divergence was associated with a glacial event that was preceded by an interglacial period putatively associated with the dispersal. Moreover, significant levels of genetic differentiation and a high number of exclusive haplotypes could be encountered even in micro-geographical scales, as in the comparisons between populations located within the same major lineage, indicating each of them may encompass independent management units. Conservation actions are certainly urgent, especially in the face of signs of a recent bottleneck.     

Network organization of interstitial connective tissue cells in the human endolymphatic duct.

The human endolymphatic duct (ED) and sac of the inner ear have been suggested to control endolymph volume and pressure. However, the physiological mechanisms for these processes remain obscure. We investigated the organization of the periductal interstitial connective tissue cells and extracellular matrix (ECM) in four freshly fixed human EDs by transmission electron microscopy and by immunohistochemistry. The unique surgical material allowed a greatly improved structural and epitopic preservation of tissue. Periductal connective tissue cells formed frequent intercellular contacts and focally occurring electron-dense contacts to ECM structures, creating a complex tissue network. The connective tissue cells also formed contacts with the basal lamina of the ED epithelium and the bone matrix, connecting the ED with the surrounding bone of the vestibular aqueduct. The interstitial connective tissue cells were non-endothelial and non-smooth muscle fibroblastoid cells. We suggest that the ED tissue network forms a functional mechanical entity that takes part in the control of inner ear fluid pressure and endolymph resorption.     

Meloidogyne incognita Surface Antigen Epitopes in Infected Arabidopsis Roots

Surface-coat epitopes of Meloidogyne incognita were detected in root tissues of Arabidopsis thaliana during migration and feeding site formation. A whole-mount root technique was used for immunolocalization of surface coat epitopes in A. thaliana, with the aid of a monoclonal antibody raised specifically against the outer surface of infective juveniles of M. incognita. The antibody, which was Meloidogyne-specific, recognized a fucosyl-bearing glycoprotein in the surface coat. During migration in host tissues the surface coat was shed, initially accumulating in the intercellular spaces next to the juvenile and later at cell junctions farther from the nematode. Upon induction of giant cell formation, the antibody bound to proximally located companion cells and sieve elements of the phloem.     

Global patterns of diversity among the specialist birds of riverine landscapes

1. Despite the growing view that biodiversity provides a unifying theme in river ecology, global perspectives on richness in riverine landscapes are limited. As a result, there is little theory or quantitative data on features that might have influenced global patterns in riverine richness, nor are there clear indications of which riverine landscapes are important to conservation at the global scale. As conspicuous elements of the vertebrate fauna of riverine landscapes, we mapped the global distributions of all of the world's specialist riverine birds and assessed their richness in relation to latitude, altitude, primary productivity and geomorphological complexity (surface configuration). 2. Specialist riverine birds, typical of high‐energy riverine landscapes and dependent wholly or partly on production from river ecosystems, occur in 16 families. They are represented by an estimated 60 species divided equally between the passerines and non‐passerines. Major radiation has occurred among different families on different continents, indicating that birds have evolved several times into the niches provided by riverine landscapes. 3. Continental richness varies from four species in Europe to 28 in Asia, with richness on the latter continent disproportionately larger than would be expected from a random distribution with respect to land area. Richness is greatest in mountainous regions at latitudes of 20–40°N in the riverine landscapes of the Himalayan mountains, where 13 species overlap in range. 4. Family, genus and species richness in specialist riverine birds all increase significantly with productivity and surface configuration (i.e. relief). However, family richness was the best single predictor of the numbers of species or genera. In keeping with the effect of surface configuration, river‐bird richness peaks globally at 1300–1400 m altitude, and most species occur typically on small, fast rivers where they feed predominantly on invertebrates. Increased lengths of such streams in areas of high relief and rainfall might have been responsible for species–area effects. 5. We propose the hypothesis that the diversity in channel forms and habitats in riverine landscapes, in addition to high temperature and primary productivity, have been prerequisites to the development of global patterns in the richness of specialist riverine organisms. We advocate tests of this hypothesis in other taxonomic groups. We draw attention, however, to the challenges of categorically defining riverine organisms in such tests because (i) rivers grade into many other habitat types across several different ecotones and (ii) `terrestrialisation' processes in riverine landscapes means that they offer habitat for organisms whose evolutionary origins are not exclusively riverine.