Immunization with N-propionyl polysialic acid–KLH conjugate in patients with small cell lung cancer is safe and induces IgM antibodies reactive with SCLC cells and bactericidal against group B meningococci

Purpose  

Polysialic acid (polySA) is a polymer side chain bound to the neural cell adhesion molecule that is extensively expressed on the surface of small cell lung cancer (SCLC) cells. In our previous study, a robust antibody response was noted in patients with SCLC after vaccination with 30 μg of keyhole limpet hemocyanin (KLH)-conjugated N-propionylated (NP-) polySA, but peripheral neuropathy and ataxia were detected in several vaccinated patients. The objectives of the current trial were to establish the lowest optimal dose and to confirm the safety of the induction of antibodies against polySA with the NP-polySA vaccine.     

Fructans from oat and rye: composition and effects on membrane stability during drying

Fructans have been implicated in the abiotic stress tolerance of many plant species, including grasses and cereals. To elucidate the possibility that cereal fructans may stabilize cellular membranes during dehydration, we used liposomes as a model system and isolated fructans from oat (Avena sativa) and rye (Secale cereale). Fructans were fractionated by preparative size exclusion chromatography into five defined size classes (degree of polymerization (DP) 3 to 7) and two size classes containing high DP fructans (DP>7 short and long). They were characterized by high performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The effects of the fructans on liposome stability during drying and rehydration were assessed as the ability of the sugars to prevent leakage of a soluble marker from liposomes and liposome fusion. Both species contain highly complex mixtures of fructans, with a DP up to 17. The two DP>7 fractions from both species were unable to protect liposomes, while the fractions containing smaller fructans were protective to different degrees. Protection showed an optimum at DP 4 and the DP 3, 4, and 5 fractions from oat were more protective than all other fractions from both species. In addition, we found evidence for synergistic effects in membrane stabilization in mixtures of low DP with DP>7 fructans. The data indicate that cereal fructans have the ability to stabilize membranes under stress conditions and that there are size and species dependent differences between the fructans. In addition, mixtures of fructans, as they occur in living cells may have protective properties that differ significantly from those of the purified fractions.     

Using Arabidopsis thaliana as a model to study subzero acclimation in small grains

The suitability of using Arabidopsis as a model plant to investigate freezing tolerance was evaluated by observing similarities to winter cereals in tissue damage following controlled freezing and determining the extent to which Arabidopsis undergoes subzero-acclimation. Plants were grown and frozen under controlled conditions and percent survival was evaluated by observing re-growth after freezing. Paraffin embedded sections of plants were triple stained and observed under light microscopy. Histological observations of plants taken 1 week after freezing showed damage analogous to winter cereals in the vascular tissue of roots and leaf axels but no damage to meristematic regions. The LT(50) of non-acclimated Arabidopsis decreased from about -6 degrees C to a minimum of about -13 degrees C after 7 days of cold-acclimation at 3 degrees C. After exposing cold-acclimated plants to -3 degrees C for 3 days (subzero-acclimation) the LT(50) was lowered an additional 3 degrees C. Defining the underlying mechanisms of subzero-acclimation in Arabidopsis may provide an experimental platform to help understand winter hardiness in economically important crop species. However, distinctive histological differences in crown anatomy between Arabidopsis and winter cereals must be taken into account to avoid misleading conclusions on the nature of winter hardiness in winter cereals.     

Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction

Renal fibrosis is the final, common pathway of end-stage renal disease. Whether and how autophagy contributes to renal fibrosis remains unclear. Here we first detected persistent autophagy in kidney proximal tubules in the renal fibrosis model of unilateral ureteral obstruction (UUO) in mice. UUO-associated fibrosis was suppressed by pharmacological inhibitors of autophagy and also by kidney proximal tubule-specific knockout of autophagy-related 7 (PT-Atg7 KO). Consistently, proliferation and activation of fibroblasts, as indicated by the expression of ACTA2/α-smooth muscle actin and VIM (vimentin), was inhibited in PT-Atg7 KO mice, so was the accumulation of extracellular matrix components including FN1 (fibronectin 1) and collagen fibrils. Tubular atrophy, apoptosis, nephron loss, and interstitial macrophage infiltration were all inhibited in these mice. Moreover, these mice showed a specific suppression of the expression of a profibrotic factor FGF2 (fibroblast growth factor 2). In vitro, TGFB1 (transforming growth factor β 1) induced autophagy, apoptosis, and FN1 accumulation in primary proximal tubular cells. Inhibition of autophagy suppressed FN1 accumulation and apoptosis, while enhancement of autophagy increased TGFB1-induced-cell death. These results suggest that persistent activation of autophagy in kidney proximal tubules promotes renal interstitial fibrosis during UUO. The profibrotic function of autophagy is related to the regulation on tubular cell death, interstitial inflammation, and the production of profibrotic factors.     

静磁场对单株人体体表正常菌生长影响的研究

本文通过40mT和120mT两种静磁场作用下表皮葡萄球菌生长过程的研究,发现试验所选强度静磁场加速了表皮葡萄球菌在对数生长期的生长速率,而在进入稳定生长期后其生长速率反而低于对照组,但就整个生长周期而言,静磁场作用下表皮葡萄球菌的总量大于对照组,表明了试验所选静磁场对表皮葡萄球菌生长有一定促进作用.     

Four flippers or two? Tetrapodal swimming with an aquatic robot

To understand how to modulate the behavior of underwater swimmers propelled by multiple appendages, we conducted surge maneuver experiments on our biologically-inspired robot, Madeleine. Robot Madeleine is a self-contained, self-propelled underwater vehicle with onboard processor, sensors and power supply. Madeleine's four flippers, oscillating in pitch, can be independently controlled, allowing us to test the impact of flipper phase on performance. We tested eight gaits, four four-flippered and four two-flippered. Gaits were selected to vary the phase, at either 0 or pi rad, between flippers on one side, producing a fore-aft interaction, or flippers on opposite sides, producing a port-starboard interaction. During rapid starting, top-speed cruising, and powered stopping, the power draw, linear acceleration and position of Madeleine were measured. Four-flippered gaits produced higher peak start accelerations than two, but did so with added power draw. During cruising, peak speeds did not vary by flipper number, but power consumption was double in four flippers compared to that of two flippers. Cost of transport (J N(-1) m(-1)) was lower for two-flippered gaits and compares favorably with that of aquatic tetrapods. Two four-flippered gaits produce the highest surge scope, a measure of the difference in peak forward and reverse acceleration. Thus four flippers produce superior surge behavior but do so at high cost; two flippers serve well for lost-cost cruising.     

A metacommmunity approach to co-occurrence patterns and the core-satellite hypothesis in a community of tropical arboreal ants

Inferring mechanisms of community assembly from co-occurrence patterns is difficult in systems where assembly processes occur at multiple spatial scales and among species with heterogeneous dispersal abilities. Here, we demonstrate that local scale analysis of co-occurrence patterns is inadequate to fully describe assembly mechanisms and instead utilize a metacommunity and core-satellite approach. We generated a co-occurrence and life-history data set for a community of twig-nesting ants on coffee plants across 36 sites within a tropical agroecosystem to test the following three hypotheses: (1) twig-nesting ant species compete for nest-sites, (2) they are structured as a metacommunity, and (3) core species show segregated patterns, while satellite species show random patterns of co-occurrence. Species were divided into four groups: core species that are well distributed regionally and dominant locally, regional dominants that are well distributed regionally but do not dominate locally, local dominants that are dominant locally but are not widely distributed, and satellites that are neither widely distributed nor dominant locally. Only the most abundant species in the community, Pseudomyrmex simplex, was classified as a core species. Regional dominants, local dominants, and satellite species show random patterns of co-occurrence. However, when P. simplex is included in the co-occurrence matrix, patterns become aggregated for all three species groupings. This suggests that P. simplex “assembles” the community by providing a core metapopulation that other species track. Analyzing co-occurrence patterns among candidate subsets of species, at multiple spatial scales, and linking them to species traits substantially improves the explanatory power of co-occurrence analyses in complex metacommunities.     

Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus

T cell receptors (TR), through their interaction with the major histocompatibility complex, play a central role in immune responsiveness and potentially immune-related disorders. We resequenced all 57 variable (V) genes in the human T cell receptor alpha and delta (TRA/TRD) locus in 40 individuals of Northern European, Mexican, African-American and Chinese descent. Two hundred and eighty-four single nucleotide polymorphisms (SNPs) were identified. The distribution of SNPs between V genes was heterogeneous, with an average of five SNPs per gene and a range of zero to 15. We describe the patterns of linkage disequilibrium for these newly discovered SNPs and compare these patterns with other emerging large-scale datasets (e.g. Perlegen and HapMap projects) to place our findings into a framework for future analysis of genotype–phenotype associations across this locus. Furthermore, we explore signatures of natural selection across V genes. We find evidence of strong directional selection at this locus as evidenced by unusually high values of F _st Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Allelic spectrum of the natural variation in CRP

With the recent completion of the International HapMap Project, many tools are in hand for genetic association studies seeking to test the common variant/common disease hypothesis. In contrast, very few tools and resources are in place for genotype–phenotype studies hypothesizing that rare variation has a large impact on the phenotype of interest. To create these tools for rare variant/common disease studies, much interest is being generated towards investing in re-sequencing either large sample sizes of random chromosomes or smaller sample sizes of patients with extreme phenotypes. As a case study for rare variant discovery in random chromosomes, we have re-sequenced ~1,000 chromosomes representing diverse populations for the gene C-reactive protein (CRP). CRP is an important gene in the fields of cardiovascular and inflammation genetics, and its size (~2 kb) makes it particularly amenable medical or deep re-sequencing. With these data, we explore several issues related to the present-day candidate gene association study including the benefits of complete SNP discovery, the effects of tagSNP selection across diverse populations, and completeness of dbSNP for CRP. Also, we show that while deep re-sequencing uncovers potentially medically relevant coding SNPs, these SNPs are fleetingly rare when genotyped in a population-based survey of 7,000 Americans (NHANES III). Collectively, these data suggest that several different types re-sequencing and genotyping approaches may be required to fully understand the complete spectrum of alleles that impact human phenotypes.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.