Nutritional composition and angiotensin converting enzyme inhibitory activity of blue lupin (Lupinus angustifolius)

AMIN BIN ISMAIL/ Chew Lye Yee// CHIN YING YEE,AZRINA BINTI AZLAN/// Gaik Theng Toh,Junus Salam Pessy The nutritional, protein and amino acid compositions of blue lupin (Lupinus angustifolius) flour were studied. The angiotensin converting enzyme (ACE) inhibitory activity of lupin protein isolate (LPI) hydrolysates prepared using Alcalase and Flavourzyme, and the Osborne protein fractions hydrolysates prepared using Alcalase were determined. Lupin flour was high in protein (43 g/100 g) and dietary fiber (34 g/100 g) but low in carbohydrate (4.8 g/100 g) and ash (3.4 g/100 g). Results from a sequential Osborne extraction procedure showed that lupin protein was comprised of 56% globulin, 26% albumin and 19% glutelin, while prolamin was only found in trace amounts. Lupin protein was high in Lys but limiting in Met. SDS-PAGE analysis suggested that protein hydrolysis catalyzed using Alcalase was more effective than Flavourzyme as shown by the presence of lower molecular weight peptides in the former. LPI hydrolysates prepared using Alcalase showed high ACE inhibitory activities with IC50 values ranging from 0.10 to 0.21 mg/ml. The results suggested that the globulin fraction was the main contributor towards the ACE inhibitory activity observed in lupin protein

Smart Mobility Cities: Connecting Bristol and Kuala Lumpur project report

Financed by the British Council Institutional Links program this Smart Mobility Cities project has opened a fascinating window on a journey of discovery linking Bristol and Kuala Lumpur. This journey was in part directed towards the realisation of Smart Mobility solutions to the socio-economic and environmental challenges of global urbanisation. Beyond this, the journey was also concerned to strengthen research and innovation partnerships between the UK and the emerging knowledge economy of Malaysia, enabling UK social scientists to collaborate on challenging global issues with international researchers and vice versa. This Smart Mobility Cities project report presents innovative, creative and yet fully practical solutions for these societal challenges. Solutions that explore a range of opportunities, whichinclude those arising from new urban governance requirements, and which are in-line with visions for sustainable urban mobility.These Smart Mobility solutions have arisen from intensive co-design and co-creation engagement with a diversity of stakeholders. Research co-production has linked the principal university partners of the University of the West of England (UWE), Bristol, and Taylor’sUniversity, Kuala Lumpur, together with the Malaysia Institute of Transport (MITRANS), Universiti Teknologi Mara, and the University Sains Malaysia (USM) in intensive engagement with stakeholder interests in both UK and Malaysia over a two-year period

BRCA1 and BRCA2 Germline Mutations in Malaysian Women with Early-Onset Breast Cancer without a Family History

BACKGROUND: In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised. METHODOLOGY: Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (<or=40 years) and no reported family history. Mutational analysis of BRCA1 and BRCA2 was conducted by full sequencing of all exons and intron-exon junctions. CONCLUSIONS: Here, we report a total of 14 BRCA1 and 17 BRCA2 sequence alterations, of which eight are novel (3 BRCA1 and 5 BRCA2). One deleterious BRCA1 mutation and 2 deleterious BRCA2 mutations, all of which are novel mutations, were identified in 3 of 37 individuals. This represents a prevalence of 2.7% and 5.4% respectively, which is consistent with other studies in other Asian ethnic groups (4-9%)

Cdc7l1

Cdc7 (Cell division cycle 7), also known as Hsk1 in fission yeast, is an important serine/threonine kinase, whose sequence is conserved from yeasts to mammals. The kinase activity of Cdc7 is regulated during the cell cycle by an activation subunit Dbf4 (also known as Dfp1/Him1 in fission yeast and ASK in mammals,) via heterodimer formation between the two. Cdc7 was first identified in budding yeast as a temperature-sensitive mutant (cdc7 ts ) defective in cell cycle progression. The budding yeast cdc7 ts cells arrest immediately before the onset of S phase at the non-permissive temperature, but resume growth and complete S phase in the absence of ongoing protein synthesis upon return to the permissive temperature. Cdc7 plays a conserved, pivotal role in triggering origin firing through phosphorylation of MCM (mini-chromosome maintenance) proteins. It facilitates the loading of Cdc45 and other replisome factors onto the pre-replicative complex, to generate active replication forks. In addition, it regulates other chromosomal transactions including DNA damage checkpoint, meiotic recombination, bypass DNA synthesis and histone functions. Selective induction of apoptosis in human cancer cells, but not in normal fibroblasts, after Cdc7 inhibition has provoked the effort in the development of Cdc7 inhibitors as potential anti-cancer drugs. Indeed, studies to date have suggested human Cdc7 as a new promising target in cancer therapy

Cdc7l1

Cdc7 (Cell division cycle 7), also known as Hsk1 in fission yeast, is an important serine/threonine kinase, whose sequence is conserved from yeasts to mammals. The kinase activity of Cdc7 is regulated during the cell cycle by an activation subunit Dbf4 (also known as Dfp1/Him1 in fission yeast and ASK in mammals,) via heterodimer formation between the two. Cdc7 was first identified in budding yeast as a temperature-sensitive mutant (cdc7 ts ) defective in cell cycle progression. The budding yeast cdc7 ts cells arrest immediately before the onset of S phase at the non-permissive temperature, but resume growth and complete S phase in the absence of ongoing protein synthesis upon return to the permissive temperature. Cdc7 plays a conserved, pivotal role in triggering origin firing through phosphorylation of MCM (mini-chromosome maintenance) proteins. It facilitates the loading of Cdc45 and other replisome factors onto the pre-replicative complex, to generate active replication forks. In addition, it regulates other chromosomal transactions including DNA damage checkpoint, meiotic recombination, bypass DNA synthesis and histone functions. Selective induction of apoptosis in human cancer cells, but not in normal fibroblasts, after Cdc7 inhibition has provoked the effort in the development of Cdc7 inhibitors as potential anti-cancer drugs. Indeed, studies to date have suggested human Cdc7 as a new promising target in cancer therapy

Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review

In advanced cancer, pain is a poor prognostic factor, significantly impacting patients’ quality of life. It has been shown that up to 30% of cancer patients in Southeast Asian countries may receive inadequate analgesia from opioid therapy. This significant under-management of cancer pain is largely due to the inter-individual variability in opioid dosage and relative efficacy of available opioids, leading to unpredictable clinical responses to opioid treatment. Single nucleotide polymorphisms (SNPs) cause the variability in opioid treatment outcomes, yet their association in Asian populations remains unclear. Therefore, this review aimed to evaluate the association of SNPs with variability in opioid treatment responses in Asian populations. A literature search was conducted in Medline and Embase databases and included primary studies investigating the association of SNPs in opioid treatment outcomes, namely pharmacokinetics, opioid dose requirements, and pain control among Asian cancer patients. The results show that CYP2D6*10 has the most clinical relevance in tramadol treatment. Other SNPs such as rs7439366 (UGT2B7), rs1641025 (ABAT) and rs1718125 (P2RX7) though significant have limited pharmacogenetic implications due to insufficient evidence. OPRM1 rs1799971, COMT rs4680 and ABCB1 (rs1045642, rs1128503, and rs2032582) need to be further explored in future for relevance in Asian populations

Sequence variants identified in the <i>BRCA1</i> gene.

<p>MS, missense; Syn, synonymous; FS, frameshift; VUS, variant of uncertain significance; BIC, Breast Information Core</p

Sequence variants identified in the <i>BRCA2</i> gene.

*<p>These sequence alterations are likely to be polymorphisms. They have been classified as benign as allelic frequency data from population studies are not currently available. MS, missense; Syn, synonymous; FS, frameshift; VUS, variant of uncertain significance; BIC, Breast Information Core</p

Molecular Mechanism of Activation of Human Cdc7 Kinase: BIPARTITE INTERACTION WITH Dbf4/ACTIVATOR OF S PHASE KINASE (ASK) ACTIVATION SUBUNIT STIMULATES ATP BINDING AND SUBSTRATE RECOGNITION*

Cdc7 is a serine/threonine kinase conserved from yeasts to human and is known to play a key role in the regulation of initiation at each replication origin. Its catalytic function is activated via association with the activation subunit Dbf4/activator of S phase kinase (ASK). It is known that two conserved motifs of Dbf4/ASK are involved in binding to Cdc7, and both are required for maximum activation of Cdc7 kinase. Cdc7 kinases possess unique kinase insert sequences (kinase insert I–III) that are inserted at defined locations among the conserved kinase domains. However, precise mechanisms of Cdc7 kinase activation are largely unknown. We have identified two segments on Cdc7, DAM-1 (Dbf4/ASK interacting motif-1; amino acids 448–457 near the N terminus of kinase insert III) and DAM-2 (C-terminal 10-amino acid segment), that interact with motif-M and motif-C of ASK, respectively, and are essential for kinase activation by ASK. The C-terminal 143-amino acid polypeptide (432–574) containing DAM-1 and DAM-2 can interact with Dbf4/ASK. Characterization of the purified ASK-free Cdc7 and Cdc7-ASK complex shows that ATP binding of the Cdc7 catalytic subunit requires Dbf4/ASK. However, the “minimum” Cdc7, lacking the entire kinase insert II and half of kinase insert III, binds to ATP and shows autophosphorylation activity in the absence of ASK. However, ASK is still required for phosphorylation of exogenous substrates by the minimum Cdc7. These results indicate bipartite interaction between Cdc7 and Dbf4/ASK subunits facilitates ATP binding and substrate recognition by the Cdc7 kinase