The effect of tripeptide tyroserleutide (YSL) on animal models of hepatocarcinoma

This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the survival time of mice transplanted with the ascitic fluid-type hepatocarcinoma H22, as well as the inhibitory effect of tyroserleutide on the human hepatocarcinoma Bel-7402 that was transplanted into nude mice. At doses of 80, 20 and 5 microg/kg/d, tyroserleutide significantly prolonged the survival of mice transplanted with H22 tumor cells, producing survival rates of 89%, 39% and 49%, respectively, which were statistically significantly different from the saline group (P < 0.05). YSL, at doses of 80, 160 and 320 microg/kg/d significantly inhibited the growth of the human hepatocarcinoma Bel-7402 tumor in nude mice, producing inhibition of 40%, 64% and 59%, respectively; this inhibition was significantly greater than that by saline (P < 0.05). HE staining and electron microscopy of the pathological changes of the tumor in nude mice showed that YSL changed the structure Bel-7402 tumor cells that were transplanted into nude mice, and also induced tumor cell apoptosis and necrosis, which could be a mechanism by which YSL inhibits the tumor growth in animal models.     

Proxy comparison in ancient peat sediments: pollen,macrofossil and plant DNA

We compared DNA, pollen and macrofossil data obtained from Weichselian interstadial (age more than 40 kyr) and Holocene (maximum age 8400 cal yr BP) peat sediments from northern Europe and used them to reconstruct contemporary floristic compositions at two sites. The majority of the samples provided plant DNA sequences of good quality with success amplification rates depending on age. DNA and sequencing analysis provided five plant taxa from the older site and nine taxa from the younger site, corresponding to 7% and 15% of the total number of taxa identified by the three proxies together. At both sites, pollen analysis detected the largest (54) and DNA the lowest (10) number of taxa, but five of the DNA taxa were not detected by pollen and macrofossils. The finding of a larger overlap between DNA and pollen than between DNA and macrofossils proxies seems to go against our previous suggestion based on lacustrine sediments that DNA originates principally from plant tissues and less from pollen. At both sites, we also detected Quercus spp. DNA, but few pollen grains were found in the record, and these are normally interpreted as long-distance dispersal. We confirm that in palaeoecological investigations, sedimentary DNA analysis is less comprehensive than classical morphological analysis, but is a complementary and important tool to obtain a more complete picture of past flora.     

‘Racism: From the Labour Movement to the Far-Right’

This report is a reflection on a recent conference, ‘Racism: From the Labour Movement to the Far-Right’, which was held at the University of Glasgow from Friday 5th to Saturday 6th September 2014. The authors discuss the main themes that the conference sought to address, consider the key highlights of the event including a summary of the opening address by Floya Anthias, and offer some suggestions as to how the initiative may be taken forward.     

Frequency and density-dependent selection on life-history strategies--a field experiment

Negative frequency-dependence, which favors rare genotypes, promotes the maintenance of genetic variability and is of interest as a potential explanation for genetic differentiation. Density-dependent selection may also promote cyclic changes in frequencies of genotypes. Here we show evidence for both density-dependent and negative frequency-dependent selection on opposite life-history tactics (low or high reproductive effort, RE) in the bank vole (Myodes glareolus). Density-dependent selection was evident among the females with low RE, which were especially favored in low densities. Instead, both negative frequency-dependent and density-dependent selection were shown in females with high RE, which were most successful when they were rare in high densities. Furthermore, selection at the individual level affected the frequencies of tactics at the population level, so that the frequency of the rare high RE tactic increased significantly at high densities. We hypothesize that these two selection mechanisms (density- and negative frequency-dependent selection) may promote genetic variability in cyclic mammal populations. Nevertheless, it remains to be determined whether the origin of genetic variance in life-history traits is causally related to density variation (e.g. population cycles).     

Laccaria bicolor aquaporin LbAQP1 is required for Hartig net development in trembling aspen (Populus tremuloides)

The development of ectomycorrhizal associations is crucial for growth of many forest trees. However, the signals that are exchanged between the fungus and the host plant during the colonization process are still poorly understood. In this study, we have identified the relationship between expression patterns of Laccaria bicolor aquaporin LbAQP1 and the development of ectomycorrhizal structures in trembling aspen (Populus tremuloides) seedlings. The peak expression of LbAQP1 was 700‐fold higher in the hyphae within the root than in the free‐living mycelium after 24 h of direct interaction with the roots. Moreover, in LbAQP1 knock‐down strains, a non‐mycorrhizal phenotype was developed without the Hartig net and the expression of the mycorrhizal effector protein MiSSP7 quickly declined after an initial peak on day 5 of interaction of the fungal hyphae with the roots. The increase in the expression of LbAQP1 required a direct contact of the fungus with the root and it modulated the expression of MiSSP7. We have also determined that LbAQP1 facilitated NO, H₂O₂ and CO₂ transport when heterologously expressed in yeast. The report demonstrates that the L. bicolor aquaporin LbAQP1 acts as a molecular signalling channel, which is fundamental for the development of Hartig net in root tips of P. tremuloides.     

Biologically active MK-801 and SKF-10,047 binding sites distinct from those in rat brain are expressed on human lung cancer cells.

We have shown previously that cultured human lung cancer cells of different histologic types express multiple opioid receptors that can regulate their growth. In this report, we show that these cells also express specific, saturable, and high-affinity binding sites (Kd approximately 1 nM) for the non-opioid phencyclidine (PCP), [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]cyclohepten-5,10-imine hydrogen maleate] (MK-801) and sigma N-allylnormetazocine (SKF-10,047) receptor ligands. Characterization of these binding sites showed them to be protein in nature and sensitive to the guanine nucleotide GTP. Pharmacological studies showed that (+) MK-801 and (+) SKF-10,047 competed with each other for their binding sites and also for the methadone binding site present in these cells. However, the mu and delta opioid ligands did not compete for (+) MK-801 and (+) SKF-10,047 binding sites. In addition, these binding sites on lung cancer cells appear to be distinct from the N-methyl D-aspartate/PCP receptor ionophore complex reported to be present in rat brain. MK-801 and SKF-10,047, at nM concentrations, were found to inhibit the growth of these cells in culture within a few hours of exposure, and this effect was irreversible after 24 h. The growth effects of these ligands could not be reversed by the opioid antagonist naloxone, suggesting involvement of nonopioid type receptors in the actions of these ligands. The abundant expression of biologically active MK-801 and SKF-10 047 binding sites in these cell lines, distinct from those in rat brain, suggests that these cell lines may prove to be a valuable source for further characterization and purification of these binding sites.     

Responses of Strawberry (Fragaria × ananassa) to Supplemental UV-B Radiation and Selenium Under Field Conditions

In greenhouse experiments, selenium (Se) has been shown to defend plants against detrimental effects of heavy UV-B radiation stress. The aim of this study was to investigate whether this positive effect can be found in open-field conditions with enhancement of UV-B radiation. In the experiment, conducted with strawberry (Fragaria×ananassa, cultivars “Jonsok” and “Polka”) over two growing seasons, plants were exposed to UV-B radiation (including UV-A) and cultivated without Se or supplied with Se added at two levels (0.1 and 1.0 mg kg⁻¹). The plants were monitored for growth, flavonoids, chlorophyll fluorescence, net photosynthesis as well as tissue and cell structure. Photosystem II was observed to be sensitive to UV-B stress under field conditions. In the leaves, a decrease in F_v/F_m was seen at the end of the growing season, implying a cumulative effect of UV-B stress. Several parameters, especially cell and tissue structures, were affected by UV-B and UV-A treatments, which proves the need for UV-A control in outdoor UV-B supplementation studies. Addition of Se did not ameliorate the harmful effects of UV-B but the lower Se-increment level increased leaf growth. The effects of UV-B and Se differed during the two experimental years, indicating the need to repeat experiments during several growing seasons.     

Mapping the idiotopes of a monoclonal anti-myoglobin antibody with syngeneic monoclonal anti-idiotypic antibodies: detection of a common idiotope

A panel of syngeneic monoclonal anti-idiotypic antibodies was prepared by immunizing A.SW mice with keyhole limpet hemocyanin-coupled A.SW monoclonal anti-myoglobin (HAL 19, IgG1) and screening the cloned hybridomas for production of IgG2 binding to idiotype but not to certain other anti-myoglobin antibodies of the same subclass in an ELISA. With these antibodies, we identified three nonoverlapping idiotopes, based on three clusters of monoclonal anti-idiotopes that mutually inhibit within each cluster, but not between clusters (Cluster I: S2, S6, S8; Cluster II: S5, S7; Cluster III: S9). Only Cluster II antibodies block the binding of myoglobin to HAL 19 and so identify a binding site-related idiotope(s). Binding of both Cluster II monoclonals (S5 and S7) to Hal 19 is inhibited by a rabbit anti-idiotype that we previously reported detects a common cross-reactive anti-myoglobin idiotope in immune sera. However, only one of these, S7, and not S5, identifies an idiotope that is present on 20 to 30% of A.SW anti-myoglobin antibodies in immune sera and ascites. The panel of syngeneic monoclonal anti-idiotype antibodies also detects new idiotopes not detected by the rabbit anti-idiotype. The development of a panel of syngeneic monoclonal anti-idiotypic antibodies to different clusters of idiotopes on the same antibody molecule, including one that identifies a major common idiotope in immune sera, should allow the analysis of possible idiotype network regulation in vivo and in vitro in a completely syngeneic system.     

Loss of assembly of the main basement membrane collagen, type IV, but not fibril-forming collagens and embryonic death in collagen prolyl 4-hydroxylase I null mice

Collagen prolyl 4-hydroxylases (C-P4Hs) catalyze the formation of the 4-hydroxyproline residues that are essential for the generation of triple helical collagen molecules. The vertebrate C-P4Hs I, II, and III are [alpha(I)]2beta2, [alpha(II)]2beta2, and [alpha(III)]2beta2 tetramers with identical beta subunits. We generated mice with targeted inactivation of the P4ha1 gene encoding the catalytic alpha subunit of C-P4H I to analyze its specific functions. The null mice died after E10.5, showing an overall developmental delay and a dilated endoplasmic reticulum in their cells. The capillary walls were frequently ruptured, but the capillary density remained unchanged. The C-P4H activity level in the null embryos and fibroblasts cultured from them was 20% of that in the wild type, being evidently due to the other two isoenzymes. Collagen IV immunofluorescence was almost absent in the basement membranes of the null embryos, and electron microscopy revealed disrupted basement membranes, while immunoelectron microscopy showed a lack of collagen IV in them. The amount of soluble collagen IV was increased in the null embryos and cultured null fibroblasts, indicating a lack of assembly of collagen IV molecules into insoluble structures, probably due to their underhydroxylation and hence abnormal conformation. In contrast, the null embryos had collagen I and III fibrils with a typical cross-striation pattern but slightly increased diameters, and the null fibroblasts secreted fibril-forming collagens, although less efficiently than wild-type cells. The primary cause of death of the null embryos was thus most likely an abnormal assembly of collagen IV.