Germline Mutations in the Polyposis-Associated Genes BMPR1A,SMAD4, PTEN,MUTYH and GREM1 Are Not Common in Individuals with Serrated Polyposis Syndrome

Background

Recent reports have observed that individuals with serrated polyps, some of whom meet the clinical diagnostic criteria for Serrated Polyposis Syndrome (SPS), are among those who carry germline mutations in genes associated with polyposis syndromes including; (1) genes known to underlie hamartomatous polyposes (SMAD4, BMPR1A, and PTEN), (2) MUTYH-associated polyposis and (3) GREM1 in Hereditary Mixed Polyposis Syndrome (HMPS). The aim of this study was to characterise individuals fulfilling the current WHO criteria for SPS for germline mutations in these polyposis-associated genes.

Methods

A total of 65 individuals with SPS (fulfilling WHO criteria 1 or 3), were recruited to the Genetics of Serrated Neoplasia study between 2000 and 2012, through multiple Genetics or Family Cancer Clinics within Australia, or from the New Zealand Familial Gastrointestinal Cancer Service. Individuals with SPS were tested for coding mutations and large deletions in the PTEN, SMAD4, and BMPR1A genes, for the MUTYH variants in exons 7 (Y179C) and 13 (G396D), and for the duplication upstream of GREM1.

Results

We found no variants that were likely to be deleterious germline mutations in the SPS cases in the PTEN, SMAD4, and BMPR1A genes. A novel variant in intron 2 (c.164+223T>C) of PTEN was identified in one individual and was predicted by in silico analysis to have no functional consequences. One further individual with SPS was found to be mono-allelic for the MUTYH G396D mutation. No individuals carried the recently reported duplication within GREM1.

Conclusions

Genes involved in the gastrointestinal hamartomatous polyposis, Hereditary Mixed Polyposis Syndrome and MUTYH-associated polyposis syndromes are not commonly altered in individuals with SPS.     

Polar body formation in Spisula oocytes: function of the peripheral aster

Activated Spisula oocytes proceed through meiotic stages rapidly and in near synchrony, providing an excellent system for analyzing polar body formation. Our previous studies suggested that cortical spreading of the metaphase peripheral aster determines spatial features of the cortical F-actin ring that is generated prior to extrusion of the polar body. We tested this hypothesis by experimentally altering the number and cortical contact patterns of peripheral asters. Such alteration was achieved by (a) lovastatin-induced arrest at metaphase I, with and without hexylene glycol modification, followed by washout; and (b) cytochalasin-D inhibition of extrusion of the first polar body, with washout before extrusion of the second polar body. Both methods induced simultaneous formation of two or more cortically spreading asters, correlated with subsequent formation of double, or even triple, overlapping F-actin rings during anaphase. Regardless of pattern, ring F-actin was deposited near regions of greatest astral microtubule density, indicating that microtubules provided a positive stimulus to which the cortex responded indiscriminately. These results strongly support the proposed causal relationship between peripheral aster spreading and biogenesis of the F-actin ring involved in polar body formation.     

The rattan trade of Northern Myanmar: Species, supplies, and sustainability

Although Myanmar exports millions of dollars of rattan cane each year, the last systematic treatment of rattans in this country was done over 100 years ago, and virtually nothing has been written about the collection and trade of this important forest resource. Here we report the results from a study of rattans in the Hukaung Valley Tiger Reserve in northern Myanmar. A total of 15 species of rattan were encountered; seven species are new records for Myanmar and two species are new to science. Inventory transects revealed that the density of commercial rattans in local forests averages 40.5 canes ≽4m long/hectare. Populations of all species appear to be actively regenerating. The current pattern of rattan exploitation, however, is largely uncontrolled and will eventually lead to resource depletion unless some form of management is implemented.     

Temperature Regulation of Endogenous Gibberellin Activity and Development of Tulipa gesneriana L

The changes in the contents of free and bound gibberellin-like activity (GA) of Tulipa gesneriana L. cv. Ralph during development under 2 temperature conditions were studied. The results show that the content of free GA of bulbs grown at 18° increased by 67% over the initial level during development. The bound GA showed a slight initial increase and was followed by a rapid decrease. In contrast, bulbs treated at 13° showed a marked decline in free GA and a 2-fold increase in the content of bound GA. However, after the transfer of these bulbs from 13° to 18° the free GA increased to the initial level while the bound GA decreased to a low level.     

Quantitative Magnetic Resonance (QMR) for Longitudinal Evaluation of Body Composition Changes With Two Dietary Regimens

We have recently reported a validation study of a prototype low‐field strength quantitative magnetic resonance (QMR) instrument for measurement of human body composition (EchoMRI‐AH). QMR was very precise, but underreported fat mass (FM) by 2–4 kg when compared to a 4‐compartment (4C) model in this cross‐sectional study. Here, we report the performance of an updated instrument in two longitudinal studies where FM was decreasing. Healthy obese volunteers were given a modest energy deficit diet for 8 weeks (study A) and obese patients with heart failure and/or at high cardiovascular risk were prescribed a low energy liquid diet for 6 weeks (study B). FM was measured at the start and end of these periods by QMR, dual‐energy X‐ray absorptiometry (DXA) and 4C. A higher proportion of the weight lost came from fat in study A compared with study B, where loss of total body water (TBW) played a greater part. The intraclass correlation between QMR and 4C estimates of FM loss (ΔFat) was 0.95, but 20 of 22 estimates of ΔFat by QMR were lower than the corresponding estimate by the 4C model. Bland–Altman analysis demonstrated that estimates of FM loss by QMR were ～1.0 and 0.7 kg lower than those obtained with 4C (P = 0.0008) and DXA (P = 0.049), respectively. Measurement precision remained high. QMR measurement should prove valuable for quantifying modest changes of FM in small trials.     

Differential Roles of Arabidopsis Dynamin-Related Proteins DRP3A,DRP3B,and DRP5B in Organelle Division

Dynamin-related proteins (DRPs) are key components of the organelle division machineries, functioning as molecular scissors during the fission process. In Arabidopsis, DRP3A and DRP3B are shared by peroxisomal and mitochondrial division, whereas the structurally-distinct DRP5B (ARC5) protein is involved in the division of chloroplasts and peroxisomes. Here, we further investigated the roles of DRP3A, DRP3B, and DRP5B in organelle division and plant development. Despite DRP5B's lack of stable association with mitochondria, drp5B mutants show defects in mitochondrial division. The drp3A-2 drp3B-2 drp5B-2 triple mutant exhibits enhanced mitochondrial division phenotypes over drp3A-2 drp3B-2, but its peroxisomal morphology and plant growth phenotypes resemble those of the double mutant. We further demonstrated that DRP3A and DRP3B form a supercomplex in vivo, in which DRP3A is the major component, yet DRP5B is not a constituent of this complex. We thus conclude that DRP5B participates in the division of three types of organelles in Arabidopsis, acting independently of the DRP3 complex. Our findings will help elucidate the precise composition of the DRP3 complex at organelle division sites, and will be instrumental to studies aimed at understanding how the same protein mediates the morphogenesis of distinct organelles that are linked by metabolism.     

Enhancing anaerobic hydrolysis of cattle manure in leachbed reactors

In this study, it is hypothesized that anaerobic hydrolysis of organic solid wastes (OSWs) in leachbed reactors can be enhanced by two approaches: (1) by increasing the porosity of the leachbed; and (2) by seeding the bed with brown-rot fungi or anaerobically digested residues. The hypothesis is verified using cattle manure as a model OSW and pistachios-half-shell as an inert additive to increase the porosity of the leachbed. The enhancement was quantified in terms of volatile fatty acid (VFA) generation and soluble COD generation. Results of this study showed that 15% more VFAs and 8% more soluble COD can be obtained at higher bed porosities and with brown-rot fungi or digested residues as the seed. Compared to a leachbed without any recirculation, porosity enhancement, nor seed addition, the VFA yield (g VFA/g manure) in a leachbed with pistachios-half-shell as porosity enhancers was 193% higher; that in a leachbed with leachate recirculation (of 4 L/day), pistachios-half-shell as porosity enhancers, and brown-rot fungi or digested sludge as seed was 230% higher.