Biological properties of a CD4 immunoadhesin

Molecular fusions of CD4, the receptor for human immunodeficiency virus (HIV), with immunoglobulin (termed CD4 immunoadhesins) possess both the gp120-binding and HIV-blocking properties of recombinant soluble CD4, and certain properties of IgG, notably long plasma half-life and Fc receptor binding. Here we show that a CD4 immunoadhesin can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) towards HIV-infected cells, although, unlike natural anti-gp120 antibodies, it does not allow ADCC towards uninfected CD4-expressing cells that have bound soluble gp120 to the CD4 on their surface. In addition, CD4 immunoadhesin, like natural IgG molecules, is efficiently transferred across the placenta of a primate. These observations have implications for the therapeutic application of CD4 immunoadhesins, particularly in the area of perinatal transmission of HIV infection.     

Modern systematics and environmental significance of stable isotopic variations in Wanxiang Cave, Wudu, Gansu, China

This paper presents the stable isotopic compositions from the cave dripwater and actively forming soda straw stalactites collected from Wanxiang Cave, Wudu, Gansu, located on the Qinghai-Tibetan Plateau and Loess Plateau transition zone, China. The δ^18Odw and δDdw of dripwater samples in the cave plot directly on the local MWL, constructed by using GNIP data from 3 sites surrounding the cave regions (Lanzhou, Xi‘an, and Chengdu), the nearest site to the cave, suggesting that there is a close relationship be-tween the δ^18Odw of the cave water and the δ^18O of the pre-cipitations. Using the measured δ^18Odw and δ^18Omc values from the mid-farthest parts from the cave entrance and the carbonate paleotemperature equation, the calculated temperatures range from 8.9 to 12.4℃, with the mean value of 10.7℃ and the temperature calculated at 8 locations in the farthest part of the cave is in the range of 10.I--12.4℃, with the mean value of 11.5℃, being consistent with the survey value(10.99℃)in the cave, slightly lower than the mean annual temperature (14.4℃) in Wudu. This suggests that modern speleothems are forming under isotopic equilibrium and their isotopic composition accurately reflects the mean annual temperature at the surface, indicating that the isotopic composition of the modern speleothems records local temperature change with credibility.     

THE STRUCTURES OF SOME MESOPHASE PITCH-BASED CARBON FIBRES

The macro-and micro-structure of two groups(high modulus and high thermalconductivity)of MP-based carbon fibres were studied using X-ray diffraction,and both scanningand transmission electron microscopy.The dominant macrostructure in cross section is of foldedpseudo-radial layers which have a tendency to form a quasi-uniform domain as the fibre modulusincreases.It is found that high thermal conductivity fibres have both missimg sector and circularcross sections(possessed predominantly by the high modulus fibre group).The microstructuralstudy indicates that apart from the fibre C700,which has a three-dimensional graphite structure,these two groups of carbon fibres all exhibit a turbostratic stacking order.Furthermore it is foundthat the turbostratic stacking thickness as determined from dark-field measurement is much largerthan the classical crystallite thickness L_c as measured from X-ray diffraction.     

Peptido-aminobenzophenones--novel latentiated benzo-1,4-diazepines.

It has been shown that cleavage of the N-terminal L-amino acids of a novel series of dipeptide derivatives of 2-aminobenzophenones occurs readily in vivo to give benzo-1,4-diazepines. Such compounds may serve as useful pro-drug forms of minor tranquilizers such as Valium.     

A novel member of the F-box/WD40 gene family, encoding dactylin, is disrupted in the mouse dactylaplasia mutant.

Early outgrowth of the vertebrate embryonic limb requires signalling by the apical ectodermal ridge (AER) to the progress zone (PZ), which in response proliferates and lays down the pattern of the presumptive limb in a proximal to distal progression. Signals from the PZ maintain the AER until the anlagen for the distal phalanges have been formed. The semidominant mouse mutant dactylaplasia (Dac) disrupts the maintenance of the AER, leading to truncation of distal structures of the developing footplate, or autopod. Adult Dac homozygotes thus lack hands and feet except for malformed single digits, whereas heterozygotes lack phalanges of the three middle digits. Dac resembles the human autosomal dominant split hand/foot malformation (SHFM) diseases. One of these, SHFM3, maps to chromosome 10q24 (Refs 6,7), which is syntenic to the Dac region on chromosome 19, and may disrupt the orthologue of Dac. We report here the positional cloning of Dac and show that it belongs to the F-box/WD40 gene family, which encodes adapters that target specific proteins for destruction by presenting them to the ubiquitination machinery. In conjuction with recent biochemical studies, this report demonstrates the importance of this gene family in vertebrate embryonic development.     

Reconstructing the early evolution of Fungi using a six-gene phylogeny

The ancestors of fungi are believed to be simple aquatic forms with flagellated spores, similar to members of the extant phylum Chytridiomycota (chytrids). Current classifications assume that chytrids form an early-diverging clade within the kingdom Fungi and imply a single loss of the spore flagellum, leading to the diversification of terrestrial fungi. Here we develop phylogenetic hypotheses for Fungi using data from six gene regions and nearly 200 species. Our results indicate that there may have been at least four independent losses of the flagellum in the kingdom Fungi. These losses of swimming spores coincided with the evolution of new mechanisms of spore dispersal, such as aerial dispersal in mycelial groups and polar tube eversion in the microsporidia (unicellular forms that lack mitochondria). The enigmatic microsporidia seem to be derived from an endoparasitic chytrid ancestor similar to Rozella allomycis, on the earliest diverging branch of the fungal phylogenetic tree.     

Allee effects and pulsed invasion by the gypsy moth

Biological invasions pose considerable threats to the world's ecosystems and cause substantial economic losses. A prime example is the invasion of the gypsy moth in the United States, for which more than $194 million was spent on management and monitoring between 1985 and 2004 alone. The spread of the gypsy moth across eastern North America is, perhaps, the most thoroughly studied biological invasion in the world, providing a unique opportunity to explore spatiotemporal variability in rates of spread. Here we describe evidence for periodic pulsed invasions, defined as regularly punctuated range expansions interspersed among periods of range stasis. We use a theoretical model with parameter values estimated from long-term monitoring data to show how an interaction between strong Allee effects (negative population growth at low densities) and stratified diffusion (most individuals disperse locally, but a few seed new colonies by long-range movement) can explain the invasion pulses. Our results indicate that suppressing population peaks along range borders might greatly slow invasion.     

Alzheimer’s disease: the impact of age-related changes in reproductive hormones

Recent findings from the Womens Health Initiative (WHI) have raised considerable concern over prolonged use of opposed and unopposed oral conjugated equine estrogen (CEE), given the increased risk of serious adverse effects, including stroke and venous thromboembolic complications. Furthermore, results from the WHI Memory Study (WHIMS) indicated that over 5 years of therapy with Prempro impaired performance on global cognitive tests and nearly doubled the risk of dementia. These surprising findings were contradictory to cumulative evidence from basic science, epidemiological and some intervention studies suggesting hormone therapy was cardioprotective and could potentially reduce the risk of dementia. This review paper focuses on the neurobiology of estrogen, summarizing the clinical evidence for neuroprotective and cognition-enhancing efficacy of estrogen. Further, the paper briefly discusses variables that may account for the unexpected findings of WHIMS, and offers suggestions for future research.