Convergent maternal care strategies in ungulates and macropods

Mammals show extensive interspecific variation in the form of maternal care. Among ungulates, there is a dichotomy between species in which offspring follow the mother (following strategy) versus species in which offspring remain concealed (hiding strategy). Here we reveal that the same dichotomy exists among macropods (kangaroos, wallabies and allies). We test three traditional adaptive explanations and one new life history hypothesis. and find very similar patterns among both ungulates and macropods. The three traditional explanations that we tested were that a ''following'' strategy is associated with (1) open habitat, (2) large mothers, and (3) gregariousness. Our new life-history hypothesis is that a following strategy'' is associated with delayed weaning, and thus with the slow end of the slow-fast mammalian life-history continuum, because offspring devote resources to locomotion rather than rapid growth. Our comparative test strongly supports the habitat structure hypothesis and provides some support for this new delayed weaning hypothesis for both ungulates and macropods. We propose that sedentary young in closed habitats benefit energetically by having milk brought to them. In open habitats, predation pressure will select against hiding. Followers will suffer slower growth to independence. Taken together, therefore, our results provide the first quantitative evidence that macropods and ungulates are convergent with respect to interspecific variation in maternal care strategy. In both clades, differences between species in the form of parental care are due to a similar interaction between habitat, social behavior, and life history.

PFG-NMR measurements of the self-diffusion coefficients of water in equilibrium poly(HEMA-co-THFMA) hydrogels

The self-diffusion coefficients for water in a series of copolymers of 2-hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA, swollen with water to their equilibrium states have been studied at 310 K using PFG-NMR. The self-diffusion coefficients calculated from the Stejskal-Tanner equation, D-obs, for all of the hydrated polymers were found to be dependent on the NMR storage time, as a result of spin exchange between the proton reservoirs of the water and the polymers, reaching an equilibrium plateau value at long storage times. The true values of the diffusion coefficients were calculated from the values of D-obs, in the plateau regions by applying a correction for the fraction of water protons present, obtained from the equilibrium water contents of the gels. The true self-diffusion coefficient for water in polyHEMA obtained at 310 K by this method was 5.5 x 10(-10) m(2) s(-1). For the copolymers containing 20% HEMA or more a single value of the self-diffusion coefficient was found, which was somewhat larger than the corresponding values obtained for the macroscopic diffusion coefficient from sorption measurements. For polyTHFMA and copolymers containing less than 20% HEMA, the PFG-NMR stimulated echo attenuation decay curves and the log-attenuation plots were characteristic of the presence of two diffusing water species. The self-diffusion coefficients of water in the equilibrium-hydrated copolymers were found to be dependent on the copolymer composition, decreasing with increasing THFMA content.

Extensive vascularization of developing mouse ovaries revealed by caveolin-1 expression

Expression screening for genes preferentially expressed in mouse fetal ovaries relative to testes identified Cav-1 as a candidate female-specific gene. Cav-1 encodes caveolin-1, a component of the cell membrane invaginations known as caveolae, which are involved in lipid regulation and signal transduction. In situ hybridization revealed high levels of Cav-1 mRNA in developing ovaries, compared with moderate or low levels in testes. Analysis of caveolin-1 protein distribution by immunofluorescence showed this difference to be due to the development of a dense and complex vascular network in the developing ovary. These observations point to a higher degree of differentiation and organization of the early stage mammalian ovary than previously suspected. (C) 2002 Wiley-Liss, Inc.

The coactivator-associated arginine methyltransferase is necessary for muscle differentiation - CARM1 coactivates myocyte enhancer factor-2

Studies with the myogenic basic helix-loop-helix and MADS box factors suggest that efficient transactivation is dependent on the recruitment of the steroid receptor coactivator (SRC) and the cofactors p300 and p300/CBP-associated factor. SRCs have been demonstrated to recruit CARM1 (coactivator-associated arginine methyltransferase-1), a member of the S-adenOSyl-L-methionine-dependent PRMTI-5 (protein-arginine N-methyltransferase-1-5) family, which catalyzes the methylation of arginine residues. This prompted us to investigate the functional role of CARM1/PRMT4 during skeletal myogenesis. We demonstrate that CARM1 and the SRC cofactor GRIP-1 cooperatively stimulate the activity of myocyte enhancer factor-2C (MEF2C). Moreover, there are direct interactions among MEF2C, GRIP-1, and CARM1. Chromatin immunoprecipitation demonstrated the in vivo recruitment of MEF2 and CARM1 to the endogenous muscle creatine kinase promoter in a differentiation-dependent manner. Furthermore, CARM1 is expressed in somites during embryogenesis and in the nuclei of muscle cells. Treatment of myogenic cells with the methylation inhibitor adenosine dialdehyde or tet-regulated CARM1 antisense expression did not affect expression of MyoD. However, inhibition of CARM1. inhibited differentiation and abrogated the expression of the key transcription factors (myogenin and MEF2) that initiate the differentiation cascade. This work clearly demonstrates that the arginine methyltransferase CARM1 potentiates myogenesis and supports the positive role of arginine methylation in mammalian differentiation.

The Phox Homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation

Recent studies have shown that phox homology (PX) domains act as phosphoinositide-binding motifs. The majority of PX domains studied show binding to phosphatidylinositol 3-monophosphate (Ptdlns(3)P), an association that allows the host protein to localize to membranes of the endocytic pathway. One issue, however, is whether PX domains may have alternative phosphoinositide binding specificities that could target their host protein to distinct subcellular compartments or allow their allosteric regulation by phosphoinositides other than PtdIns(3)P. It has been reported that the PX domain of sorting nexin 1 (SNX1) specifically binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3) (Zhong, Q., Lazar, C. S., Tronchere, H., Sato, T., Meerloo, T., Yeo, M., Songyang, Z., Emr, S. D., and Gill, G. N. (2002) Proc. Natl. Acad. Sci. U. S. A. 99,6767-6772). In the present study, we have shown that whereas SNX1 binds PtdIns(3,4,5)P-3 in protein:lipid overlay assays, in liposomes-based assays, binding is observed to PtdIns(3)P and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P-2) but not to PtdIns(3,4,5)P-3. To address the significance of PtdIns(3,4,5)P-3 binding, we examined the subcellular localization of SNX1 under conditions in which plasma membrane PtdIns(3,4,5)P-3 levels were significantly elevated. Under these conditions, we failed to observe association of SNX1 with this membrane. However, consistent with the binding to PtdIns(3)P and PtdIns(3,5)P-2 being of more physiological significance was the observation that the association of SNX1 with an early endosomal compartment was dependent on a 3-phosphoinositide-binding PX domain and the presence of PtdIns(3)P on this compartment. Finally, we somal association of SNX1 is important for its ability to regulate the targeting of internalized epidermal growth factor receptor for lysosomal degradation.

Expression of specific glycoconjugates in both primary and secondary olfactory pathways in BALB/C mice

Binding of cell surface carbohydrates to their receptors specifically promotes axon growth and synaptogenesis in select regions of the developing nervous system. In some cases these interactions depend upon cell-cell adhesion mediated by the same glycoconjugates present on the surface of apposing cells or their processes. We have previously shown that the plant lectin Dolichos biflorus agglutinin (DBA) binds to: a subpopulation of mouse primary olfactory neurons whose axons selectively fasciculate prior to terminating in the olfactory bulb. In the present study, we investigated whether these glycoconjugates were also expressed by postsynaptic olfactory neurons specifically within the olfactory pathway. We show here for the first time that DBA ligands were expressed both by a subset of primary olfactory neurons as well as by the postsynaptic mitral/tufted cells in BALB/C mice. These glycoconjugates were first detected on mitral/tufted cell axons during the early postnatal period, at a time when there is considerable synaptogenesis and synaptic remodelling in the primary olfactory cortex. This is one of the few examples of the selective expression of molecules in contiguous axon tracts in the mammalian nervous system. These results suggest that glycoconjugates recognized by DBA may have a specific role in the formation and maintenance of neural connections within a select functional pathway in the brain. J. Comp. Neurol. 443:213-225, 2002. (C) 2002 Wiley-Liss, Inc.

Lamproites from Gaussberg, Antarctica: Possible transition zone melts of Archaean subducted sediments

Petrogenetic models for the origin of lamproites are evaluated using new major element, trace element, and Sr, Nd, and Pb isotope data for Holocene lamproites from the Gaussberg volcano in the East Antarctic Shield. Gaussberg lamproites exhibit very unusual Pb isotope compositions (Pb-206/Pb-204 = 17.44-17.55 and Pb-207/Pb-204 = 15.56-15.63), which in common Pb isotope space plot above mantle evolution lines and to the left of the meteorite isochron. Combined with very unradiogenic Nd, such compositions are shown to be inconsistent with an origin by melting of sub-continental lithospheric mantle. Instead, a model is proposed in which late Archaean continent-derived sediment is subducted as K-hollandite and other ultra-high-pressure phases and sequestered in the Transition Zone (or lower mantle) where it is effectively isolated for 2-3 Gyr. The high Pb-207/Pb-204 ratio is thus inherited from ancient continent-derived sediment, and the relatively low Pb-206/Pb-204 ratio is the result of a single stage of U/Pb fractionation by subduction-related U loss during slab dehydration. Sr and Nd isotope ratios, and trace element characteristics (e.g. Nb/Ta ratios) are consistent with sediment subduction and dehydration-related fractionation. Similar models that use variable time of isolation of subducted sediment can be derived for all lamproites. Our interpretation of lamproite sources has important implications for ocean island basalt petrogenesis as well as the preservation of geochemically anomalous reservoirs in the mantle.

Expression and role of roundabout-1 in embryonic Xenopus forebrain

The receptor Roundabout-1 (Robo1) and its ligand Slit are known to influence axon guidance and central nervous system (CNS) patterning in both vertebrate and nonvertebrate systems. Although Robo-Slit interactions mediate axon guidance in the Drosophila CNS, their role in establishing the early axon scaffold in the embryonic vertebrate brain remains unclear. We report here the identification and expression of a Xenopus Robo1 orthologue that is highly homologous to mammalian Robo1. By using overexpression studies and immunohistochemical and in situ hybridization techniques, we have investigated the role of Robo1 in the development of a subset of neurons and axon tracts in the Xenopus forebrain. Robo1 is expressed in forebrain nuclei and in neuroepithelial cells underlying the main axon tracts. Misexpression of Robo1 led to aberrant development of axon tracts as well as the ectopic differentiation of forebrain neurons. These results implicate Robo1 in both neuronal differentiation and axon guidance in embryonic vertebrate forebrain. (C) 2002 Wiley-Liss, Inc.

Differential sorting and fate of endocytosed GPI-anchored proteins

In this paper, we studied the fate of endocytosed glycosylphosphatidyl inositol anchored proteins (GPI-APs) in mammalian cells, using aerolysin, a bacterial toxin that binds to the GPI anchor, as a probe. We find that GPI-APs are transported down the endocytic pathway to reducing late endosomes in BHK cells, using biochemical, morphological and functional approaches. We also find that this transport correlates with the association to raft-like membranes and thus that lipid rafts are present in late endosomes (in addition to the Golgi and the plasma membrane). In marked contrast, endocytosed GPI-APs reach the recycling endosome in CHO cells and this transport correlates with a decreased raft association. GPI-APs are, however, diverted from the recycling endosome and routed to late endosomes in CHO cells, when their raft association is increased by clustering seven or less GPI-APs with an aerolysin mutant. We conclude that the different endocytic routes followed by GPI-APs in different cell types depend on the residence time of GPI-APs in lipid rafts, and hence that raft partitioning regulates GPI-APs sorting in the endocytic pathway.

Current concepts in central nervous system regeneration

A dictum long-held has stated that the adult mammalian brain and spinal cord are not capable of regeneration after injury. Recent discoveries have, however, challenged this dogma. In particular, a more complete understanding of developmental neurobiology has provided an insight into possible ways in which neuronal regeneration in the central nervous system may be encouraged. Knowledge of the role of neurotrophic factors has provided one set of strategies which may be useful in enhancing CNS regeneration. These factors can now even be delivered to injury sites by transplantation of genetically modified cells. Another strategy showing great promise is the discovery and isolation of neural stem cells from adult CNS tissue. It may become possible to grow such cells in the laboratory and use these to replace injured or dead neurons. The biological and cellular basis of neural injury is of special importance to neurosurgery, particularly as therapeutic options to treat a variety of CNS diseases becomes greater. (C) 2002 Published by Elsevier Science Ltd.

Mathematical modelling of schistosomiasis japonica: comparison of control strategies in the People's Republic of China

We present the first mathematical model on the transmission dynamics of Schistosoma japonicum. The work extends Barbour's classic model of schistosome transmission. It allows for the mammalian host heterogeneity characteristic of the S. japonicum life cycle, and solves the problem of under-specification of Barbour's model by the use of Chinese data we are collecting on human-bovine transmission in the Poyang Lake area of Jiangxi Province in China. The model predicts that in the lake/marshland areas of the Yangtze River basin: (1) once-early mass chemotherapy of humans is little better than twice-yearly mass chemotherapy in reducing human prevalence. Depending on the heterogeneity of prevalence within the population, targeted treatment of high prevalence groups, with lower overall coverage, can be more effective than mass treatment with higher overall coverage. Treatment confers a short term benefit only, with prevalence rising to endemic levels once chemotherapy programs are stopped (2) depending on the relative contributions of bovines and humans, bovine treatment can benefit humans almost as much as human treatment. Like human treatment, bovine treatment confers a short-term benefit. A combination of human and bovine treatment will dramatically reduce human prevalence and maintains the reduction for a longer period of time than treatment of a single host, although human prevalence rises once treatment ceases; (3) assuming 75% coverage of bovines, a bovine vaccine which acts on worm fecundity must have about 75% efficacy to reduce the reproduction rate below one and ensure mid-term reduction and long-term elimination of the parasite. Such a vaccination program should be accompanied by an initial period of human treatment to instigate a short-term reduction in prevalence, following which the reduction is enhanced by vaccine effects; (4) if the bovine vaccine is only 45% efficacious (the level of current prototype vaccines) it will lower the endemic prevalence, but will not result in elimination. If it is accompanied by an initial period of human treatment and by a 45% improvement in human sanitation or a 30% reduction in contaminated water contact by humans, elimination is then possible. (C) 2002 Elsevier Science B.V. All rights reserved.

Charting the course of ovarian development in vertebrates

The decision of the embryonic gonad to differentiate as either a testis or an ovary is a critical step in vertebrate development. The molecular basis of this decision has been the focus of much study, particularly over the past decade. Here we contrast the knowledge of early gonadal development and the switch to testis differentiation with the lack of molecular understanding of ovarian development at early stages. We review current knowledge regarding mechanisms of ovarian morphogenesis and propose a model for the hierarchical control of development of the fetal ovary, incorporating the few genes already known to be important and several signals or factors that are hypothesised to exist in the early ovary.

Secretory pathway of trypanosomatid parasites

The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Tryanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles it? the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory), transport and protein glycosylation that may be exploited in developing new antiparasite drugs.

Plasma growth hormone and growth hormone-binding protein during development in the marsupial brushtail possum (Trichosurus vulpecula)

Plasma concentrations of growth hormone (GH) were measured in the brushtail possum (Trichosurus vulpecula) pouch young from 25 through to 198 days post-partum (n=71). GH concentrations were highest early in pouch life (around 100 ng/ml), and thereafter declined in an exponential fashion to reach adult concentrations (10.8 +/- 1.8 ng/ml; n=21) by approximately 121-145 days post-partum, one to two months before the young is weaned. Growth hormone-binding protein (GHBP), which has been shown to modify the cellular actions of GH in eutherian mammals, was identified for the first time in a marsupial. Based on size exclusion gel filtration, possum GHBP had an estimated molecular mass of approximate to 65 kDa, similar to that identified in other mammalian species, and binding of I-125-labelled human GH (hGH) was displaced by excess hGH (20 mug). An immunoprecipitation method, in which plasma GHBP was rendered polyethylene glycol precipitable with a monoclonal antibody to the rabbit GHBP/GH receptor (MAb 43) and labelled with I-125-hGH, was used to quantitate plasma GHBP by Scatchard analysis in the developing (pooled plasma samples) and adult (individual animals) possums. Binding affinity (K-a) values in pouch young aged between 45 and 54 and 144 and 153 days post-partum varied between 1.0 and 2.4 x 10(9)/M, which was slightly higher than that in adult plasma (0.96 +/- 0.2 x 10(9)/M, n = 6). Binding capacity (B-max) values increased from non-detectable levels in animals aged 25-38 days post-partum to reach concentrations around half that seen in the adult (1.4 +/- 0.2 x 10(-9) M) by about 117 days post-partum and remained at this level until 153 days post-partum. Therefore, in early pouch life when plasma GH concentrations are highest, the very low concentrations of GHBP are unlikely to be important in terms of competing with GH-receptor for ligand or altering the half-life of circulating GH.

Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.