Electron-donating para-methoxy converts a benzamide-isoquinoline derivative into a highly Sigma-2 receptor selective ligand

The sigma-2 (σ2) receptor has been suggested to be a promising target for pharmacological interventions to curb tumor progression. Development of σ2-specific ligands, however, has been hindered by lack of understanding of molecular determinants that underlie selective ligand-σ2 interactions. Here we have explored effects of electron donating and withdrawing groups on ligand selectivity for the σ2 versus σ1 receptor using new benzamide-isoquinoline derivatives. The electron-donating methoxy group increased but the electron-withdrawing nitro group decreased σ2 affinity. In particular, an extra methoxy added to the para-position (5e) of the benzamide phenyl ring of 5f dramatically improved (631 fold) the σ2 selectivity relative to the σ1 receptor. This para-position provided a sensitive site for effective manipulation of the sigma receptor subtype selectivity using either the methoxy or nitro substituent. Our study provides a useful guide for further improving the σ2-over-σ1 selectivity of new ligands.     

Prenatal diagnosis in a mentally retarded woman with mosaic ring chromosome 18

We present a pregnant woman with mental retardation and mosaic for ring 18 referred for prenatal diagnosis. Major clinical features included short stature with clinodactyly in feet, foot deformity and club feet, hypotonia, kyphosis, and absence of breast development, low set ears, high arched palate, dental decay and speech disorder. Prenatal diagnosis was carried. Using amniocentesis. The fetus had a normal karyotype described as 46,XX. The fetus was evaluated for clinical features after delivery; she was healthy with no abnormal clinical characterizations.     

Fire history of a prairie/forest boundary: more than 250 years of frequent fire in a North American tallgrass prairie

Questions: Most modern fire‐prone landscapes have experienced disruptions of their historic fire regimes. Are the primary tallgrass prairies of the Flint Hills reflective of a history of continuous fire occurrence? Did fire frequency, severity, size and seasonality change in connection with changes in land use? Has fire occurrence been related to drought conditions? Location: Edges of Cross Timbers forest stands at the Tallgrass Prairie Preserve (TGPP) in the Flint Hills of Osage County, Oklahoma, USA. Methods: Cross‐sections of 76 Quercus stellata were collected from Cross Timbers stands at or near the grassland edge in the TGPP. Dendrochronological methods were used to identify years of formation for tree rings and fire scars. Superposed epoch analysis was used to evaluate the effect of drought conditions on fire occurrence. Results: Fires were recorded in 46.6% of the years between 1729 and 2005. In 41 cross‐sections at one site, the mean fire interval between 1759 and 2003 was 2.59 years, with fire interval decreasing from a mean fire interval of 3.76 years in the early part of the record to 2.13 years in modern times. No extended periods without fire were recorded in the study area. Drought conditions had no significant effect on fire occurrence. Conclusions: In contrast with many fire‐prone landscapes worldwide, the prairies of the Flint Hills have experienced no recent fire suppression or exclusion. Changes in fire frequency mark transitions in land use, primarily from being traditionally used by Native Americans to being managed for cattle production.     

Temperature‐growth divergence in white spruce forests of Old Crow Flats,Yukon Territory,and adjacent regions of northwestern North America

We present a new 23‐site network of white spruce ring‐width chronologies near boreal treeline in Old Crow Flats, Yukon Territory, Canada. Most chronologies span the last 300 years and some reach the mid‐16th century. The chronologies exhibit coherent growth patterns before the 1930s. However, since the 1930s, they diverge in trend and exhibit one of two contrasting, but well‐replicated patterns we call Group 1 and Group 2. Over the instrumental period (1930–2007) Group 1 sites were inversely correlated with previous‐year July temperatures while Group 2 sites were positively correlated with growth‐year June temperatures. At the broader northwestern North America (NWNA) scale, we find that the Group 1 and Group 2 patterns are common to a number of white spruce chronologies, which we call NWNA 1 and NWNA 2 chronologies. The NWNA 1 and NWNA 2 chronologies also share a single coherent growth pattern prior to their divergence (ca. 1950s). Comparison of the NWNA 1/NWNA 2 chronologies against gridded 20th‐century temperatures for NWNA and reconstructed northern hemisphere summer temperatures (ad 1300–2000) indicates that all sites responded positively to temperature prior to the mid‐20th century (at least back to ad 1300), but that some changed to a negative response (NWNA 1) while others maintained a positive response (NWNA 2). The spatial extent of divergence implies a large‐scale forcing. As the divergence appears to be restricted to the 20th century, we suggest that the temperature response shift represents a moisture stress caused by an anomalously warm, dry 20th‐century climate in NWNA, as indicated by paleoclimatic records. However, because some sites do not diverge and are located within a few kilometres of divergent sites, we speculate that site‐level factors have been important in determining the susceptibility of sites to the large‐scale drivers of divergence.     

Potato Cell Plasma Membrane Receptors to Ring Rot Pathogen Extracellular Polysaccharides

The interaction of extracellular polysaccharides (EPS) of the potato ring rot bacterial pathogen Clavibacter michiganensis ssp. sepedonicus (Spieck. et Kott.) Skaptason et Burkh. (Cms) with protoplasts isolated both from leaf cells of plants grown in vitro and microsomal membrane fractions obtained from cell suspension cultures of two potato (Solanum tuberosum L.) cultivars contrasted by their resistance to this pathogen was studied. The EPS intensively bind to protoplast surfaces and microsomal membranes of the susceptible cultivar but not to those of the resistant cultivar. Treatment with protease, excess of unlabelled EPS, and with dextran, did not lead to the binding of fluorochrome‐labelled EPS to protoplasts and microsomal membranes (from both cultivars). It is proposed that (a) a great number of receptors to EPS Cms are present in the plasma membranes of potato cells of susceptible cultivars, (b) these receptors contain proteinaceous sites exposed on the external side of the plasma membrane which participate in EPS binding, and (c) the plasma membranes of cells of resistant cultivars contain a small but sufficient quantity of receptors to EPS able to induce defensive responses in plants.     

Neue,chlorsubstituierte thiophenacetylenverbindungen mit ungewöhnlicher struktur aus Helichrysum-arten

The investigation of two further Helichryswn species afforded in addition to known constituents three new thiophene compounds with unusual structures. A biogenetic scheme of aromatic ring formation for this new type of chlorine containing compounds is proposed. Most probably, the pyran ring of the chloroenol ether is transformed to an aromatic ring by dehydrogenation, hydrolysis and intramolecular aldol condensation.     

Aromatase inhibition abolishes courtship behaviours in the ring dove (Streptopelia risoria) and reduces androgen and progesterone receptors in the hypothalamus and anterior pituitary gland

The aim of this study was to determine in the ring dove, the effects of aromatase inhibition on the expression of aggressive courtship and nest-soliciting behaviours in relation to the distribution of cells containing immunoreactive androgen (AR) and progesterone (PR) receptor in the hypothalamus and pituitary gland. Isolated sexually experienced ring doves were transferred in opposite sex pairs to individual breeding cages, and then injected with the aromatase inhibitor, fadrozole (four males and four females), or saline vehicle (four males and four females) for 3 days at 12 hourly intervals. Saline-injected control males displayed aggressive courtship behaviours (bow-cooing and hop-charging) and nest-soliciting throughout the study, and control females displayed nest-soliciting. By day 3, fadrozole treatment resulted in the disappearance of all these behaviours and in a decrease or disappearance of AR and PR in the anterior pituitary gland, and in the nucleus preopticus paraventricularis magnocellularis (PPM), nucleus preopticus medialis (POM), nucleus hypothalami lateralis posterioris (PLH), and ventral, lateral and dorsal nucleus tuberalis in the hypothalamus (VTu, LTu, DTu). In the nucleus preopticus anterior (POA), fadrozole treatment decreased AR in both sexes and decreased PR in females but not in males. Cells containing co-localized nuclear AR and PR were found in all hypothalamic areas examined, and in the anterior pituitary gland. Fadrozole is suggested to reduce the local availability of estrogen required indirectly for the induction of AR, and except in cells containing PR in the male POA, for the direct induction of PR. It is suggested that aggressive courtship behaviour is terminated by “cross talk” between aromatase-independent PR and aromatase-dependent AR co-localized in neurons in the POA. Aromatase-independent PR may increase in the male POA in response to visual cues provided by a partner. Aromatase-dependent PR in the POM, and basal hypothalamus may play a role in the facilitatory effect of progesterone on estrogen-induced nest-orientated behaviours. (Mol Cell Biochem 276: 193–204, 2005)     

Biotransformation of biphenyl by the filamentous fungus <Emphasis Type="Italic">Talaromyces helicus</Emphasis>

The filamentous fungusTalaromyces helicus , isolated from oil-contaminated sludge, oxidizes biphenyl via 4-hydroxybiphenyl to the dihydroxylated derivatives 4,4-dihydroxybiphenyl and 3,4-dihydroxybiphenyl, which, to a certain extent, are converted to glycosyl conjugates. The sugar moiety of the conjugate formed from 4,4-dihydroxybiphenyl was identified as glucose. Further metabolites: 2-hydroxybiphenyl, 2,5-dihydroxylated biphenyl, and the ring cleavage product 4-phenyl-2-pyrone-6-carboxylic acid accumulated only in traces. From these results the main pathway for biotransformation of biphenyl in T. helicus could be proposed to be the excretion of dihydroxylated derivatives (>75%) and their glucosyl conjugates (<25%).     

Origin and evolution of the chloroplast division machinery

Chloroplasts were originally established in eukaryotes by the endosymbiosis of a cyanobacterium; they then spread through diversification of the eukaryotic hosts and subsequent engulfment of eukaryotic algae by previously nonphotosynthetic eukaryotes. The continuity of chloroplasts is maintained by division of preexisting chloroplasts. Like their ancestors, chloroplasts use a bacterial division system based on the FtsZ ring and some associated factors, all of which are now encoded in the host nuclear genome. The majority of bacterial division factors are absent from chloroplasts and several new factors have been added by the eukaryotic host. For example, the ftsZ gene has been duplicated and modified, plastid-dividing (PD) rings were most likely added by the eukaryotic host, and a member of the dynamin family of proteins evolved to regulate chloroplast division. The identification of several additional proteins involved in the division process, along with data from diverse lineages of organisms, our current knowledge of mitochondrial division, and the mining of genomic sequence data have enabled us to begin to understand the universality and evolution of the division system. The principal features of the chloroplast division system thus far identified are conserved across several lineages, including those with secondary chloroplasts, and may reflect primeval features of mitochondrial division. Shin-ya Miyagishima is the recipient of the Botanical Society Award for Young Scientists, 2004.