Biomarkers: in combination they may do better

The field of biomarkers is a growing one, particularly in osteoarthritis (OA). OA is the most common disabling condition in older persons and a major cause of morbidity. While the debate continues about which of the involved tissues - cartilage, bone or synovium - is the most important in OA aetiology, there is no doubt that the three develop abnormalities in concert; perhaps a truly useful biomarker will reflect just that. While efforts continue to identify reliable biomarkers useful for characterising the status, prognosis and measurement of treatment response in OA, combining existing biomarkers to improve their accuracy looks promising.     

Bayesian Modeling of the Yeast SH3 Domain Interactome Predicts Spatiotemporal Dynamics of Endocytosis Proteins

SH3 domains are peptide recognition modules that mediate the assembly of diverse biological complexes. We scanned billions of phage-displayed peptides to map the binding specificities of the SH3 domain family in the budding yeast, Saccharomyces cerevisiae. Although most of the SH3 domains fall into the canonical classes I and II, each domain utilizes distinct features of its cognate ligands to achieve binding selectivity. Furthermore, we uncovered several SH3 domains with specificity profiles that clearly deviate from the two canonical classes. In conjunction with phage display, we used yeast two-hybrid and peptide array screening to independently identify SH3 domain binding partners. The results from the three complementary techniques were integrated using a Bayesian algorithm to generate a high-confidence yeast SH3 domain interaction map. The interaction map was enriched for proteins involved in endocytosis, revealing a set of SH3-mediated interactions that underlie formation of protein complexes essential to this biological pathway. We used the SH3 domain interaction network to predict the dynamic localization of several previously uncharacterized endocytic proteins, and our analysis suggests a novel role for the SH3 domains of Lsb3p and Lsb4p as hubs that recruit and assemble several endocytic complexes.     

Dynamic nature of a wheat centromere with a functional gene

Centromeric regions of higher eukaryotes are comprised mainly of tandem and non-tandem repeat sequences with variable copy number, spacing, order and orientation; are heterochromatic in nature, and are believed to be devoid of actively transcribing genes. Here, we report an actively transcribing wheat homolog of HSP70 gene that maps in the functional wheat centromere, and copy number of which seems to change in response to centromeric breaks. The HSP70 gene physically maps on the short arm of chromosomes 1A and 1D of Chinese Spring (CS) and 1R of rye. Whereas, on chromosome 1B in both ‘CS’ and Pavon background, the gene maps in the functional centromere as evident from its presence in both cytologically confirmed true ditelosomic lines Dt1BS and Dt1BL. Sequence comparison of 11 ESTs showed three sequence patterns suggesting that all three homoeologous copies of the gene are expressing. The cDNA-single stranded conformation polymorphism analysis confirmed expression of the ‘CS’ 1B copy of the gene. Observed in two independently developed Dt1BL lines, the 1B copy number of the gene showed three to fivefold increase in response to chromosomal breaks around the centromere. Putative gene duplications seem to involve large chromosomal segments as only one of the ten restriction enzymes used for DNA gel-blot analysis showed unique extra fragment band in the Dt1BL line. Further investigations are warranted to uncover the nature and mechanism of these duplications.     

Pilot scale production of functional foods using red palm olein: Antioxidant,vitamins’ stability and sensory quality during storage

The objective of this research work was to produce acceptable quality functional foods, namely, extruded snacks, digestive biscuits and pan bread, on a pilot scale, using vitamin E and β-carotene-rich red palm olein (RPOL) and red palm shortening (RPS). These products were evaluated for their chemical composition and sensory quality along with the antioxidants and vitamin contents during the six months of storage at room temperature (22 ± 1 °C). Extruded snacks and digestive biscuits prepared with RPOL and RPS were found to be good sources of these antioxidant vitamins. The average β-carotene content of the control and test snacks at the end of six months of storage ranged from 26.8 to 56.1 mg/kg fat, and from 430.9 to 468.9 mg/kg fat, respectively. The total vitamin E content in control and test snacks made in Plant No. 1 decreased after six months of storage from 786.1 to 704.4 mg/kg fat, and from 765.1 to 695.4 mg/kg fat, respectively. As expected, the total tocotrienol content was four to five times higher than the total tocopherols in control biscuits. The RPOL containing 600–750 ppm of carotenes (mainly α- and β-carotenes), 710–774 ppm of vitamin E, was found to be suitable for industrial application in producing acceptable quality pan bread, digestive biscuits and snacks. These functional foods contained significant amounts of β-carotene and total vitamin E, indicating the possibility of producing such foods rich in these two of the important antioxidant vitamins coming from a natural source. The research findings strongly indicate that good-quality pan bread, extruded snacks and digestive biscuits can successfully be produced to offer healthier eating choices to the consumers of this region, thereby promoting better health and productivity among the population.     

A hydrogen bond regulates slow motions in ubiquitin by modulating a β-turn flip

Proteins exist as conformational ensembles composed of multiple interchanging substates separated by kinetic barriers. Interconverting conformations are often difficult to probe, owing to their sparse population and transient nature. Here, we report the identification and characterization of a subset of conformations in ubiquitin that participate in microsecond-to-millisecond motions in the amides of Ile23, Asn25, and Thr55. A novel side chain to the backbone hydrogen bond that regulates these motions has also been identified. Combining our NMR studies with the available X-ray data, we have unearthed the physical process underlying slow motions—the interconversion of a type I into a type II β-turn flip at residues Glu51 through Arg54. Interestingly, the dominant conformer of wild-type ubiquitin observed in solution near neutral pH is only represented by about 22% of the crystal structures. The conformers generated as a result of the dynamics of the hydrogen bond appear to be correlated to ligand recognition by ubiquitin.