Glioma-associated endothelial cells show evidence of replicative senescence

The innately programmed process of replicative senescence has been studied extensively with respect to cancer, but primarily from the perspective of tumor cells overcoming this stringent innate barrier and acquiring the capacity for unlimited proliferation. In this study, we focus on the potential role of replicative senescence affecting the non-transformed endothelial cells of the blood vessels within the tumor microenvironment. Based on the well-documented aberrant structural and functional features of blood vessels within solid tumors, we hypothesized that tumor-derived factors may lead to premature replicative senescence in tumor-associated brain endothelial cells (TuBEC). We show here that glioma tissue, but not normal brain tissue, contains cells that express the signature of replicative senescence, senescence-associated beta-galactosidase (SA-beta-gal), on CD31-positive endothelial cells. Primary cultures of human TuBEC stain for SA-beta-gal and exhibit characteristics of replicative senescence, including increased levels of the cell cycle inhibitors p21 and p27, increased resistance to cytotoxic drugs, increased growth factor production, and inability to proliferate. These data provide the first demonstration that tumor-derived brain endothelial cells may have reached an end-stage of differentiation known as replicative senescence and underscore the need for anti-angiogenic therapies to target this unique tumor-associated endothelial cell population.     

Conflict over condition‐dependent sex allocation can lead to mixed sex‐determination systems

Theory suggests that genetic conflicts drive turnovers between sex‐determining mechanisms, yet these studies only apply to cases where sex allocation is independent of environment or condition. Here, we model parent–offspring conflict in the presence of condition‐dependent sex allocation, where the environment has sex‐specific fitness consequences. Additionally, one sex is assumed to be more costly to produce than the other, which leads offspring to favor a sex ratio less biased toward the cheaper sex in comparison to the sex ratio favored by mothers. The scope for parent–offspring conflict depends on the relative frequency of both environments: when one environment is less common than the other, parent–offspring conflict can be reduced or even entirely absent, despite a biased population sex ratio. The model shows that conflict‐driven invasions of condition‐independent sex factors (e.g., sex chromosomes) result either in the loss of condition‐dependent sex allocation, or, interestingly, lead to stable mixtures of condition‐dependent and condition‐independent sex factors. The latter outcome corresponds to empirical observations in which sex chromosomes are present in organisms with environment‐dependent sex determination. Finally, conflict can also favor errors in environmental perception, potentially resulting in the loss of condition‐dependent sex allocation without genetic changes to sex‐determining loci.     

Ants farm subterranean aphids mostly in single clone groups - an example of prudent husbandry for carbohydrates and proteins?

ABSTRACT: BACKGROUND: Mutualistic interactions are wide-spread but the mechanisms underlying their evolutionary stability and ecological dynamics remain poorly understood. Cultivation mutualisms in which hosts consume symbionts occur in phylogenetically diverse groups, but often have symbiont monocultures for each host. This is consistent with the prediction that symbionts should avoid coexistence with other strains so that host services continue to benefit relatives, but it is less clear whether hosts should always favor monocultures and what mechanisms they might have to manipulate symbiont diversity. Few mutualisms have been studied in sufficient genetic detail to address these issues, so we decided to characterize symbiont diversity in the complex mutualism between multiple root aphid species and Lasius flavus ants. After showing elsewhere that three of these aphid species have low dispersal and mostly if not exclusively asexual reproduction, we here investigate aphid diversity within and between ant nest mounds. RESULTS: The three focal species (Geoica utricularia, Forda marginata and Tetraneura ulmi) had considerable clonal diversity at the population level. Yet more than half of the ant mounds contained just a single aphid species, a significantly higher percentage than expected from a random distribution. Over 60% of these single-species mounds had a single aphid clone, and clones tended to persist across subsequent years. Whenever multiple species/clones cooccurred in the same mound, they were spatially separated with more than 95% of the aphid chambers containing individuals of a single clone. CONCLUSIONS: L. flavus "husbandry" is characterized by low aphid "livestock" diversity per colony, especially at the nest-chamber level, but it lacks the exclusive monocultures known from other cultivation mutualisms. The ants appear to eat most of the early instar aphids, so that adult aphids are unlikely to face limited phloem resources and scramble competition with other aphids. We suggest that such culling of carbohydrate-providing symbionts for protein ingestion may maintain maximal host yield per aphid while also benefitting the domesticated aphids as long as their clone-mates reproduce successfully. The cost-benefit logic of this type of polyculture husbandry has striking analogies with human farming practices based on slaughtering young animals for meat to maximize milk-production by a carefully regulated adult livestock population.     

Identifying protein-protein interfacial residues in heterocomplexes using residue conservation scores

Identifying protein–protein interfaces is crucial for structural biology. Because of the constraints in wet experiments, many computational methods have been proposed. Without knowing any information about the partner chains, a new method of predicting protein–protein interaction interface residues purely based on evolutionary information in heterocomplexes is proposed here. Unlike traditional approaches using multiple sequence alignment profiles to represent the conservation level for each residue, we make predictions based on the concept of residue conservation scores so that the dimension of the feature vector for each residue can be drastically reduced, at least 20 times less than conventional methods. Based on the representation approach, a simple linear discriminant function is used to make predictions, so the computational complexity of the whole prediction procedure can also be greatly decreased. By testing our approach on 69 heterocomplex chains, experimental results demonstrate the performance of our approach is indeed superior to current existing methods.     

模拟微重力环境对昆明小鼠早期胚胎体外发育的影响（简报）

In order to investigate the development of Kunming mouse preimplantation embryos cultured in vitro under simulated microgravtiy, one-cell and 4-cell embryos of Kunming mouse (Fertilization In Situ) were cultured in CZB or KSOM media under simulated microgravity or normal gravity environment respectively. The results showed that under normal gravity, the percentage of passing 2-cell development block embryos was not different in CZB with in KSOM, but the percentage of blastocysts was lower in CZB than that in KSOM significantly. The percentages of passing 2-cell development block embryos and blastocysts in CZB or KSOM were lower under simulated microgravity than those under normal gravity. It is suggested that the frequency of early embryonic lethality is possibly increased by simulated microgravity.     

High-affinity five/six-letter DNA aptamers with superior specificity enabling the detection of dengue NS1 protein variants beyond the serotype identification

Genetic alphabet expansion of DNA by introducing unnatural bases (UBs), as a fifth letter, dramatically augments the affinities of DNA aptamers that bind to target proteins. To determine whether UB-containing DNA (UB-DNA) aptamers obtained by affinity selection could spontaneously achieve high specificity, we have generated a series of UB-DNA aptamers (K_D: 27−182 pM) targeting each of four dengue non-structural protein 1 (DEN-NS1) serotypes. The specificity of each aptamer is remarkably high, and the aptamers can recognize the subtle variants of DEN-NS1 with at least 96.9% amino acid sequence identity, beyond the capability of serotype identification (69−80% sequence identities). Our UB-DNA aptamers specifically identified two major variants of dengue serotype 1 with 10-amino acid differences in the DEN-NS1 protein (352 aa) in Singaporeans’ clinical samples. These results suggest that the high-affinity UB-DNA aptamers generated by affinity selection also acquire high target specificity. Intriguingly, one of the aptamers contained two different UBs as fifth and sixth letters, which are essential for the tight binding to the target. These two types of unnatural bases with distinct physicochemical properties profoundly expand the potential of DNA aptamers. Detection methods incorporating the UB-DNA aptamers will facilitate precise diagnoses of viral infections and other diseases.     

Adhesive and conformational behaviour of mycolic acid monolayers

We have studied the pH-dependent interaction between mycolic acid (MA) monolayers and hydrophobic and hydrophilic surfaces using molecular (colloidal probe) force spectroscopy. In both cases, hydrophobic and hydrophilic monolayers (prepared by Langmuir-Blodgett and Langmuir-Schaefer deposition on silicon or hydrophobized silicon substrates, respectively) were studied. The force spectroscopy data, fitted with classical DLVO (Derjaguin, Landau, Verwey, and Overbeek) theory to examine the contribution of electrostatic and van der Waals forces, revealed that electrostatic forces are the dominant contribution to the repulsive force between the approaching colloidal probe and MA monolayers. The good agreement between data and the DLVO model suggest that beyond a few nm away from the surface, hydrophobic, hydration, and specific chemical bonding are unlikely to contribute to any significant extent to the interaction energy between the probe and the surface. The pH-dependent conformation of MA molecules in the monolayer at the solid-liquid interface was studied by ellipsometry, neutron reflectometry, and with a quartz crystal microbalance. Monolayers prepared by the Langmuir-Blodgett method demonstrated a distinct pH-responsive behaviour, while monolayers prepared by the Langmuir-Schaefer method were less sensitive to pH variation. It was found that the attachment of water molecules plays a vital role in determining the conformation of the MA monolayers.     

Biology of the western pygmy perch,Edelia vittata,and comparisons with two other teleost species endemic to south-western Australia

Synopsis This paper provides data on the movements, spawning times and localities, size and age composition, growth and diet of the western pygmy perch,Edelia vittata, in a south-western Australian river. The results of this study are compared with those recorded previously for two other locally endemic species (Galaxias occidentalis andBostockia porosa) to ascertain the extent to which these three species utilise the same resources, and whether they are similarly adapted to the highly seasonal flow regime. A total of 3396Edelia vittata was collected with a 3 mm mesh seine net from the Collie River in south-western Australia at 3–6 week intervals over a period of 26 months. During the winter, fish moved from the river into either adjacent flood waters or tributary creeks. The trends shown by gonadosomatic indices, oocyte growth and prevalence of post-ovulatory follicles, demonstrate that spawning takes place between late winter and late spring (July–November). Sexual maturity was attained by both sexes at the end of the first year of life. Although 99% of the fish belonged to the 0+, 1+ and 2+ age classes, representatives of the 3+, 4+ and 5+ age classes were also caught. The respective von Bertalanffy growth curve parameters for L, K and t₀ were 54.9, 1.178 and -0.210 for males and 57.9, 1.124 and -0.198 for females. At the end of the first and second years of life, the lengths predicted from the von Bertalanffy growth equations were 42 mm ( 0.8 g) and 51 mm ( 1.4 g) for males and 43 mm ( 0.9 g) and 53 mm ( 1.6 g) for females. The diet consisted of a wide range of small benthic invertebrates, especially dipteran larvae, ostracods and cyclopoid copepods. The peak time, duration and predominant locality of spawning, the time of day when maximum activity occurs and the diet ofEdelia vittata differs from those previously recorded forGalaxias occidentalis andBostockia porosa. These differences would be likely to minimize any potential competition amongst these three species. The growth rates, age at first sexual maturity and pattern of oocyte development also differ amongst the three species.     

Biology of the western minnow,Galaxias occidentalis Ogilby (Teleostei : Galaxiidae), in a south-western Australian river

The size and age composition, growth and diet of the western minnow, Galaxias occidentalis, in the southern branch of the Collie River in south-western Australia were determined from samples collected at approximately monthly intervals between January 1984 and December 1986. The prominent, narrow hyaline zone on otoliths was shown to be formed annually and thus valid for ageing these fish. An examination of the otoliths of 4711 fish indicated that 69.2 and 26.8% of the fish caught belonged to the 0 + and I + age classes, respectively. While the vast majority of the remaining fish represented the II + age class, a few III + and IV + and one V + fish were also recorded. Growth was seasonal, being greatest in spring and autumn and effectively ceasing in winter. Females began to grow faster than males during their first autumn of life. The respective mean lengths of males and females were 70 and 75 mm at the end of the first year and 90 and 100 mm at the end of the second year. The largest fish caught was a III + female measuring 163 mm and weighing 32.0 g. The respective von Bertalanffy growth curve parameters for L, K and t₀ were 109, 0.758 and - 0.338 for males, and 124, 0.762 and - 0.223 for females. Although the diet of G. occidentalis was always dominated by small terrestrial fauna, and particularly insects, conspicuous seasonal differences were found between the more important of the other components. Data on body size, growth and diet of G. occidentalis are compared with those recorded for other galaxiids.