Improving starch and fibre in wheat grain for human health

Reducing the prevalence of diet- related diseases, including obesity and type 2 diabetes, is a major challenge for health professionals, food manufacturers and governments in both developed and developing countries. Cereals are key targets in meeting this challenge as they are staple foods throughout the world and major sources of energy (derived principally from starch) and dietary fibre. Wheat is the staple cereal in the UK and Europe, and the UK Biotechnology and Biological Sciences Research Council (BBSRC)- supported Designing Future Wheat programme is focused on manipulating the content and composition of starch and fibre to improve health impacts, including reducing the glycaemic response and improving fermentation in the colon. This work is contributing to the development of improved cultivars by breeders and foods by processors. It is also increasing our understanding of the behaviour of these components in the human gastrointestinal (GI) tract and will contribute to the establishment of targets and recommendations for regulatory authorities

Loss of starch synthase IIIa changes starch molecular structure and granule morphology in grains of hexaploid bread wheat.

Starch synthase III plays a key role in starch biosynthesis and is highly expressed in developing wheat grains. To understand the contribution of SSIII to starch and grain properties, we developed wheat ssIIIa mutants in the elite cultivar Cadenza using in silico TILLING in a mutagenized population. SSIIIa protein was undetectable by immunoblot analysis in triple ssIIIa mutants carrying mutations in each homoeologous copy of ssIIIa (A, B and D). Loss of SSIIIa in triple mutants led to significant changes in starch phenotype including smaller A-type granules and altered granule morphology. Starch chain-length distributions of double and triple mutants indicated greater levels of amylose than sibling controls (33.8% of starch in triple mutants, and 29.3% in double mutants vs. 25.5% in sibling controls) and fewer long amylopectin chains. Wholemeal flour of triple mutants had more resistant starch (6.0% vs. 2.9% in sibling controls) and greater levels of non-starch polysaccharides; the grains appeared shrunken and weighed ~ 11% less than the sibling control which was partially explained by loss in starch content. Interestingly, our study revealed gene dosage effects which could be useful for fine-tuning starch properties in wheat breeding applications while minimizing impact on grain weight and quality

The Metallicity of High Redshift Galaxies: The Abundance of Zinc in 34 Damped Lyman Alpha Systems from z = 0.7 to 3.4

We report new observations of ZnII and CrII absorption lines in 10 damped \lya systems (DLAs), mostly at redshift z_{abs} \simgt 2.5 . By combining these results with those from our earlier survey (Pettini et al. 1994) and other recent data, we construct a sample of 34 measurements (or upper limits) of the Zn abundance relative to hydrogen [Zn/H]; the sample includes more than one third of the total number of DLAs known. The plot of the abundance of Zn as a function of redshift reinforces the two main findings of our previous study. (1) Damped \lya systems are mostly metal-poor, at all redshifts sampled; the column density weighted mean for the whole data set is [Zn/H] $= -1.13 \pm 0.38$ (on a logarithmic scale), or approximately 1/13 of solar. (2) There is a large spread, by up to two orders of magnitude, in the metallicities we measure at essentially the same redshifts. We propose that damped \lya systems are drawn from a varied population of galaxies of different morphological types and at different stages of chemical evolution, supporting the idea of a protracted epoch of galaxy formation. At redshifts z \simgt 2 the typical metallicity of the damped \lya systems is in agreement with expectations based on the consumption of HI gas implied by the recent measurements of $\Omega_{DLA}$ by Storrie-Lombardi et al. (1996a), and with the metal ejection rates in the universe at these epochs deduced by Madau (1996) from the ultraviolet luminosities of high redshift galaxies revealed by deep imaging surveys. There are indications in our data for an increase in the mean metallicity of the damped \lya systems from $z > 3$ to $\approx 2$, consistent with the rise in the comoving star formation rate indicated by the relative numbers of $U$ and $B$ drop-outs in the Hubble Deep Field. Although such comparisons are still tentative, it appears that these different avenues for exploring the early evolution of galaxies give a broadly consistent picture.Comment: 51 pages, LaTeX, 9 Postscript Figures. Accepted for publication in the Astrophysical Journa

Effect of semolina pudding prepared from starch branching enzyme IIa and b mutant wheat on glycaemic response in vitro and in vivo: a randomised controlled pilot study

Refined starchy foods are usually rapidly digested, leading to poor glycaemic control, but not all starchy foods are the same. Complex carbohydrates like resistant starch (RS) have been shown to reduce the metabolic risk factors for chronic diseases such as hyperglycaemia and overweight. The aim of the project was to develop a semolina-based food made from a starch branching enzyme II (sbeIIa/b-AB) durum wheat mutant with a high RS content and to measure its glycaemic index using a double-blind randomised pilot study. We report here the amylose, RS and non-starch polysaccharide concentration of raw sbeIIa/b-AB and wild-type control (WT) semolina. We measured RS after cooking to identify a model food for in vivo testing. Retrograded sbeIIa/b-AB semolina showed a higher RS concentration than the WT control (RS = 4.87 ± 0.6 g per 100 g, 0.77 ± 0.34 g per 100 g starch DWB, respectively), so pudding was selected as the test food. Ten healthy participants consumed ∼50 g of total starch from WT and sbeIIa/b-AB pudding and a standard glucose drink. Capillary blood glucose concentrations were measured in the fasting and postprandial state (2 h): incremental area-under-the-curve (iAUC) and GI were calculated. We found no evidence of difference in GI between sbeIIa/b-AB pudding and the WT control, but the starch digestibility was significantly lower in sbeIIa/b-AB pudding compared to the WT control in vitro (C90 = 33.29% and 47.38%, respectively). Based on these results, novel sbeIIa/b-AB wheat foods will be used in future in vivo studies to test the effect of different RS concentrations and different food matrices on glycaemia

The Stem Cell Phenotype of Aggressive Breast Cancer Cells

Aggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of oncology of effectively targeting heterogeneous tumor cells expressing a variety of markers, especially those associated with a stem cell phenotype. This dilemma is especially relevant in breast cancer, where therapy is based on traditional classification schemes, including histological criteria, differentiation status, and classical receptor markers. However, not all patients respond in a similar manner to standard-of-care therapy, thereby necessitating the need to identify and evaluate novel biomarkers associated with the difficult-to-target stem cell phenotype and drug resistance. Findings related to the convergence of embryonic and tumorigenic signaling pathways have identified the embryonic morphogen Nodal as a promising new oncofetal target that is reactivated only in aggressive cancers, but not in normal tissues. The work presented in this paper confirms previous studies demonstrating the importance of Nodal as a cancer stem cell molecule associated with aggressive breast cancer, and advances the field by providing new findings showing that Nodal is not targeted by standard-of-care therapy in breast cancer patients. Most noteworthy is the linkage found between Nodal expression and the drug resistance marker ATP-binding cassette member 1 (ABCA1), which may provide new insights into developing combinatorial approaches to overcome drug resistance and disease recurrence

The Stem Cell Phenotype of Aggressive Breast Cancer Cells

Aggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of oncology of effectively targeting heterogeneous tumor cells expressing a variety of markers, especially those associated with a stem cell phenotype. This dilemma is especially relevant in breast cancer, where therapy is based on traditional classification schemes, including histological criteria, differentiation status, and classical receptor markers. However, not all patients respond in a similar manner to standard-of-care therapy, thereby necessitating the need to identify and evaluate novel biomarkers associated with the difficult-to-target stem cell phenotype and drug resistance. Findings related to the convergence of embryonic and tumorigenic signaling pathways have identified the embryonic morphogen Nodal as a promising new oncofetal target that is reactivated only in aggressive cancers, but not in normal tissues. The work presented in this paper confirms previous studies demonstrating the importance of Nodal as a cancer stem cell molecule associated with aggressive breast cancer, and advances the field by providing new findings showing that Nodal is not targeted by standard-of-care therapy in breast cancer patients. Most noteworthy is the linkage found between Nodal expression and the drug resistance marker ATP-binding cassette member 1 (ABCA1), which may provide new insights into developing combinatorial approaches to overcome drug resistance and disease recurrence

Characterization of a Novel Cutaneous Human Papillomavirus Genotype HPV-125

The DNA genome of a novel HPV genotype, HPV-125, isolated from a hand wart of an immuno-competent 19-year old male was fully cloned, sequenced and characterized. The full genome of HPV-125 is 7,809-bp in length with a GC content of 46.4%. By comparing the nucleotide sequence of the complete L1 gene, HPV-125 is phylogenetically placed within cutaneotrophic species 2 of Alphapapillomaviruses, and is most closely related to HPV-3 and HPV-28. HPV-125 has a typical genomic organization of Alphapapillomaviruses and contains genes coding for five early proteins, E6, E7, E1, E2 and E4 and two late capsid proteins, L1 and L2. The genome contains two non-coding regions: the first located between the L1 and E6 genes (nucleotide positions 7,137–7,809, length 673-bp) and the second between genes E2 and L2 (nucleotide positions 3,757–4,216, length 460-bp). The E6 protein of HPV-125 contains two regular zinc-binding domains at amino acid positions 29 and 102, whereas the E7 protein exhibits one such domain at position 50. HPV-125 lacks the regular pRb-binding core sequence within its E7 protein. In order to assess the tissue predilection and clinical significance of HPV-125, a quantitative type-specific real-time PCR was developed. The 95% limit-of-detection of the assay was 2.5 copies per reaction (range 1.7–5.7) and the intra- and inter-assay coefficients of variation were 0.47 and 2.00 for 100 copies per reaction, and 1.15 and 2.15 for 10 copies per reaction, respectively. Testing of a representative collection of HPV-associated mucosal and cutaneous benign and malignant neoplasms and hair follicles (a total of 601 samples) showed that HPV-125 is a relatively rare HPV genotype, with cutaneous tropism etiologically linked with sporadic cases of common warts

Supermassive Black Holes in Galactic Nuclei: Past, Present and Future Research

This review discusses the current status of supermassive black hole research, as seen from a purely observational standpoint. Since the early '90s, rapid technological advances, most notably the launch of the Hubble Space Telescope, the commissioning of the VLBA and improvements in near-infrared speckle imaging techniques, have not only given us incontrovertible proof of the existence of supermassive black holes, but have unveiled fundamental connections between the mass of the central singularity and the global properties of the host galaxy. It is thanks to these observations that we are now, for the first time, in a position to understand the origin, evolution and cosmic relevance of these fascinating objects.Comment: Invited Review, 114 pages. Because of space requirements, this version contains low resolution figures. The full resolution version can be downloaded from http://www.physics.rutgers.edu/~lff/publications.htm

Obscured Activity: AGN, Quasars, Starbursts and ULIGs observed by the Infrared Space Observatory

Some of the most active galaxies in the Universe are obscured by large quantities of dust and emit a substantial fraction of their bolometric luminosity in the infrared. Observations of these infrared luminous galaxies with the Infrared Space Observatory (ISO) have provided a relatively unabsorbed view to the sources fuelling this active emission. The improved sensitivity, spatial resolution and spectroscopic capability of ISO over its predecessor Infrared Astronomical Satellite (IRAS), has enabled significant advances in the understanding of the infrared properties of active galaxies. ISO surveyed a wide range of active galaxies which, in the context of this review, includes those powered by intense bursts of star-formation as well as those containing a dominant active galactic nucleus (AGN). Mid infrared imaging resolved for the first time the dust enshrouded nuclei in many nearby galaxies, while a new era in infrared spectroscopy was opened by probing a wealth of atomic, ionic and molecular lines as well as broad band features in the mid and far infrared. This was particularly useful since it resulted in the understanding of the power production, excitation and fuelling mechanisms in the nuclei of active galaxies including the intriguing but so far elusive ultraluminous infrared galaxies. Detailed studies of various classes of AGN and quasars greatly improved our understanding of the unification scenario. Far-infrared imaging and photometry also revealed the presence of a new very cold dust component in galaxies and furthered our knowledge of the far-infrared properties of faint starbursts, ULIGs and quasars. We summarise almost nine years of key results based upon ISO data spanning the full range of luminosity and type of active galaxies.Comment: Accepted for publication in 'ISO science legacy - a compact review of ISO major achievements', Space Science Reviews - dedicated ISO issue. To be published by Springer in 2005. 62 pages (low resolution figures version). Higher resolution PDFs available from http://users.physics.uoc.gr/~vassilis/papers/VermaA.pdf or http://www.iso.vilspa.esa.es/science/SSR/Verma.pd

Unusual quasars from the Sloan Digital Sky Survey selected by means of Kohonen self-organising maps

We exploit the spectral archive of the Sloan Digital Sky Survey (SDSS) Data Release 7 to select unusual quasar spectra. The selection method is based on a combination of the power of self-organising maps and the visual inspection of a huge number of spectra. Self-organising maps were applied to nearly 10^5 spectra classified as quasars by the SDSS pipeline. Particular attention was paid to minimise possible contamination by rare peculiar stellar spectral types. We present a catalogue of 1005 quasars with unusual spectra. This large sample provides a useful resource for both studying properties and relations of/between different types of unusual quasars and selecting particularly interesting objects. The spectra are grouped into six types. All these types turn out to be on average more luminous than comparison samples of normal quasars after a statistical correction is made for intrinsic reddening. Both the unusual broad absorption line (BAL) quasars and the strong iron emitters have significantly lower radio luminosities than normal quasars. We also confirm that strong BALs avoid the most radio-luminous quasars. Finally, we create a sample of quasars similar to the two "mysterious" objects discovered by Hall et al. (2002) and briefly discuss the quasar properties and possible explanations of their highly peculiar spectra. (Abstract modified to match the arXiv format)Comment: Added reference to section 6; a few typos corrected; corrections according to the version published in Astronomy and Astrophysic