Lysianadioic acid, a carboxypeptidase B inhibitor from Lysiana subfalcata

A new natural product, lysianadioic acid, was isolated from the plant Lysiana subfalcata as a carboxypeptidase B (CPB) inhibitor. It is a potent inhibitor of CPB with an IC(50) of 0.36 microM. This is the first known example of a small molecule CPB inhibitor isolated from plant origin. Its structure was determined by NMR spectroscopy.     

Small-molecule inhibitors of the cancer target, isoprenylcysteine carboxyl methyltransferase, from Hovea parvicalyx

Isoprenylcysteine carboxyl methyltransferase (Icmt) is enzyme target in anticancer drug discovery. An Icmt natural product high-throughput screening campaign was conducted and a hit extract from the roots of Hovea parvicalyx was identified. 2'-Methoxy-3'-prenyl-licodione and 2'-methoxy-3',3'-diprenyl-licodione, two prenylated beta-hydroxychalcone compounds, together with the known flavanone (S)-glabrol, were isolated and identified as bioactive constituents. Their structures were determined largely by 1D and 2D NMR spectroscopy.     

Trinucleotide cassettes increase diversity of T7 phage-displayed peptide library

Background  

Amino acid sequence diversity is introduced into a phage-displayed peptide library by randomizing library oligonucleotide DNA. We recently evaluated the diversity of peptide libraries displayed on T7 lytic phage and M13 filamentous phage and showed that T7 phage can display a more diverse amino acid sequence repertoire due to differing processes of viral morphogenesis.     

Almost total protection from age-related macular degeneration by haplotypes of the Regulators of Complement Activation

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It has been proposed that the polymorphism encoding Y402H (T1277C) in the complement factor H gene (CFH) is one of the main determinants of disease. We genotyped the polymorphism at a number of loci in the region encompassing the Regulators of Complement Activation (RCA) on chromosome 1, including T1277C SNP, in 187 patients and 146 controls. Haplotypes have been classified as protective (P) or susceptible (S) with respect to AMD. This included the identification of an S haplotype with a T at 1277. The results show that no single locus should be assumed to be directly responsible for AMD, but rather argue for the existence of RCA haplotypes, which can be assigned meaningful predictive values for AMD. We conclude that the critical sequences are within a region 450 kb centromeric to 128 kb telomeric of CFH.     

Foliar Mn accumulation in eastern Australian herbarium specimens: prospecting for ��new�� Mn hyperaccumulators and potential applications in taxonomy

Background and Aims

The analysis of herbarium specimens has previously been used to prospect for ‘new’ hyperaccumulators, while the use of foliar manganese (Mn) concentrations as a taxonomic tool has been suggested. On the basis of their geographic and taxonomic affiliations to known Mn hyperaccumulators, six eastern Australian genera from the Queensland Herbarium collection were sampled for leaf tissue analyses.

Methods

ICP-OES was used to measure Mn and other elemental concentrations in 47 species within the genera Austromyrtus, Lenwebbia, Gossia (Myrtaceae), Macadamia (Proteaceae), Maytenus and Denhamia (Celastraceae).

Key Results

The resulting data demonstrated (a) up to seven ‘new’ Mn hyperaccumulators, mostly tropical rainforest species; (b) that one of these ‘new’ Mn hyperaccumulators also had notably elevated foliar Ni concentrations; (c) evidence of an interrelationship between foliar Mn and Al uptake among the Macadamias; (d) considerable variability of Mn hyperaccumulation within Gossia; and (e) the possibility that Maytenus cunninghamii may include subspecies.

Conclusions

Gossia bamagensis, G. fragrantissima, G. sankowsiorum, G. gonoclada and Maytenus cunninghamii were identified as ‘new’ Mn hyperaccumulators, while Gossia lucida and G. shepherdii are possible ‘new’ Mn hyperaccumulators. Of the three Myrtaceae genera examined, Mn hyperaccumulation appears restricted to Gossia, supporting its recent taxonomic revision. In the context of this present investigation and existing information, a reassesment of the general definition of Mn hyperaccumulation may be warranted. Morphological variation of Maytenus cunninghamii at two extremities was consistent with variation in Mn accumulation, indicating two possible ‘new’ subspecies. Although caution should be exercised in interpreting the data, surveying herbarium specimens by chemical analysis has provided an effective means of assessing foliar Mn accumulation. These findings should be followed up by field studies.Key words: Gossia bamagensis, G. fragrantissima, G. sankowskiorum, G. gonoclada, G. lucida, G. shepherdii, Maytenus cunninghamii, Mn hyperaccumulator     

The involucrin genes of the mouse and the rat: study of their shared repeats

The involucrin genes of the mouse (Mus musculus) and the rat (Rattus norvegicus) have been cloned and sequenced. The coding region of each gene contains, at site P, a segment of repeats homologous to that of other nonanthropoid mammals. In contrast to the repeats of species belonging to different mammalian orders, many individual repeats of the mouse and the rat can be matched. Both before and after the divergence of the two species, these repeats have been the site of systematic alterations in nucleotide sequence. One of the alterations is the correction of nucleotides of one repeat by those of another. Corrected nucleotides may be closely linked to flanking nucleotides that are uncorrected; the systematic correction process therefore appears to be due to gene conversion. There is a stretch of 18 reiterated CAGs in the segment of repeats of the Mus gene; most of these reiterations were introduced recently, supporting the idea that the gene was generated originally from poly CAG. An antiserum to a synthetic peptide encoded by the segment of repeats of the Mus gene reveals differentiation- specific expression of the gene in the epidermis.      

Role of lysophosphatidic acid in the retinal pigment epithelium and photoreceptors

The human retina is a complex structure of organised layers of specialised cells that support the transmission of light signals to the visual cortex. The outermost layer of the retina, the retinal pigment epithelium (RPE), forms part of the blood retina barrier and is implicated in many retinal diseases. Lysophosphatidic acid (LPA) is a bioactive lipid exerting pleiotropic effects in various cell types, during development, normal physiology and disease. Its producing enzyme, AUTOTAXIN (ATX), is highly expressed by the pigmented epithelia of the human eye, including the RPE. Using human pluripotent stem cell (hPSC)-derived retinal cells, we interrogated the role of LPA in the human RPE and photoreceptors. hPSC-derived RPE cells express and synthesize functional ATX, which is predominantly secreted apically of the RPE, suggesting it acts in a paracrine manner to regulate photoreceptor function. In RPE cells, LPA regulates tight junctions, in a receptor-dependent mechanism, with an increase in OCCLUDIN and ZONULA OCCLUDENS (ZO)-1 expression at the cell membrane, accompanied by an increase in the transepithelial resistance of the epithelium. High concentration of LPA decreases phagocytosis of photoreceptor outer segments by the RPE. In hPSC-derived photoreceptors, LPA induces morphological rearrangements by modulating the actin myosin cytoskeleton, as evidenced by Myosin Light Chain l membrane relocation. Collectively, our data suggests an important role of LPA in the integrity and functionality of the healthy retina and blood retina barrier.