Molecular and Genome Evolution in the Malesian Slipper Orchids (Paphiopedilum section Barbata).

PhDPaphiopedilum section Barbata (Cypripedioideae: Orchidaceae) is an evolutionarily young and charismatic group of terrestrial orchids native to the Himalayas, Indochina and Malesia. It contains several interesting species complexes, variable chromosome numbers (2n=28-42) and genome sizes (2C=55-70 pg) with hybrid speciation suspected on the basis of morphological data. In Chapter 1, I introduce Paphiopedilum and review existing literature on the group. In Chapter 2, I ask: what are the evolutionary relationships within section Barbata? I answer this by sequencing four plastid (ycf1, matK, psa-ycf3ex3 and trnF(GAA)-ndhJ) and two low copy nuclear gene (Xdh and CHS) regions. Analysing the phylogenetic signals revealed patterns of gene tree incongruence and geographical groupings that suggest historical and on-going hybridisation. In Chapter 3, I ask: what biogeographical processes are driving diversification of section Barbata? To answer this I estimate the age of section Barbata from a dated BEAST phylogeny of cloned Xdh sequences and analyse it in relation to the geographical history of Southeast Asia. This revealed that section Barbata arose c. 6.3 Mya (95% HPD range=4.0-8.8 Mya) and that diversification is primarily driven by hybridisation, vicariance and dispersal facilitated by glacial-interglacial cycles of sea-level fluctuations in SE Asia, and possibly chromosomal changes. In Chapter 4, I ask: what genomic changes are occurring in section Barbata? I approach this by characterising repetitive DNA sequences in representative taxa and analyse them against new genome size estimates and published chromosome numbers. The results show that Paphiopedilum genomes are comprised of 61.1-71.5% repetitive DNA, and 28.9-39.5% single or low-copy DNA that is possibly derived from ancient repetitive elements. These findings suggest that a low-rate of repetitive DNA removal, rather than proliferation of any particular family of repetitive element, is driving genome evolution in the group. Finally in Chapter 5, I present my hypotheses on speciation processes in Paphiopedilum and outline avenues for future work.Commonwealth Scholarship Emily Holmes Scholarship

Kesediaan pensyarah teknikal terhadap pelaksanaan School Enterprise di kolej vokasional wilayah Utara

Pelaksanaan School Enterprise merupakan salah satu aktiviti pendidikan berteraskan bidang keusahawanan yang dijalankan di Kolej Vokasional pada masa ini. Program School Enterprise yang dilaksanakan di Kolej Vokasional juga merupakan salah satu elemen pengajaran dan pembelajaran yang memberikan peluang kepada para pensyarah dan pelajar khususnya untuk melalui pengalaman sebenar dalam dunia perniagaan serta mengaplikasikan konsep dan teori pendekatan perniagaan yang dipelajari ke situasi yang sebenar. Para pensyarah dilihat sebagai individu yang bertanggungjawab dalam menjayakan pelaksanaan School Enterprise ini. Oleh itu, kajian ini dijalankan bagi mengenal pasti tahap kesediaan para pensyarah dalam pelaksanaan School Enterprise di empat buah Kolej Vokasional Wilayah Utara Semenanjung iaitu KV Alor Setar, KV Sungai Petani 2, KV Arau dan KV Kangar. Persepsi terhadap kesediaan para pensyarah dilihat daripada aspek pengetahuan, amalan dan kemahiran. Seramai 100 orang para pensyarah daripada empat buah Kolej Vokasional Wilayah Utara dipilih secara rawak bagi menjawab soal selidik yang diberikan. Analisis data ini melibatkan skor min dan sisihan piawai untuk menentukan skor min serta ANOVA untuk mencari perbezaan pada aspek yang dikehendaki. Didapati purata skor min kesediaan pensyarah KV di Wilayah Utara daripada aspek amalan (min=3.97) dan pengetahuan (min=3.796) serta kemahiran (min=3.821) adalah tinggi. Hal ini menunjukkan persepsi tahap kesediaan para pensyarah daripada sudut pengetahuan, amalan dan kemahiran berada pada tahap yang tinggi terhadap pelaksanaan School Enterprise. Hal ini disebabkan kebanyakan pensyarah KV telah bersedia melaksanakan program School Enterprise namun terdapat kekangan seperti bebanan tugas dan kerja di KV yang memaksa para pensyarah mendominasikan tugas pentadbiran berbanding program yang berkisarkan pada keusahawanan ini. Kesimpulannya, kajian ini menunjukkan tidak terdapat perbezaan yang signifikan mengenai kesediaan pensyarah teknikal terhadap pelaksanaan School Enterprise di Kolej Vokasional Wilayah Utara

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

The identification of novel Mycobacterium tuberculosis DHFR inhibitors and the investigation of their binding preferences by using molecular modelling

It is an urgent need to develop new drugs for Mycobacterium tuberculosis (Mtb), and the enzyme, dihydrofolate reductase (DHFR) is a recognised drug target. The crystal structures of methotrexate binding to mt- and h-DHFR separately indicate that the glycerol (GOL) binding site is likely to be critical for the function of mt-DHFR selective inhibitors. We have used in silico methods to screen NCI small molecule database and a group of related compounds were obtained that inhibit mt-DHFR activity and showed bactericidal effects against a test Mtb strain. The binding poses were then analysed and the influence of GOL binding site was studied by using molecular modelling. By comparing the chemical structures, 4 compounds that might be able to occupy the GOL binding site were identified. However, these compounds contain large hydrophobic side chains. As the GOL binding site is more hydrophilic, molecular modelling indicated that these compounds were failed to occupy the GOL site. The most potent inhibitor (compound 6) demonstrated limited selectivity for mt-DHFR, but did contain a novel central core (7H-pyrrolo[3,2-f]quinazoline-1,3-diamine), which may significantly expand the chemical space of novel mt-DHFR inhibitors. Collectively, these observations will inform future medicinal chemistry efforts to improve the selectivity of compounds against mt-DHFR

Association of maternal Vitamin D status with glucose tolerance and caesarean section in a multi-ethnic Asian cohort: the growing up in Singapore towards healthy outcomes study

10.1371/journal.pone.0142239PLoS ONE10111-16GUSTO (Growing up towards Healthy Outcomes

Genomic insights into rapid speciation within the world’s largest tree genus Syzygium

Species radiations, despite immense phenotypic variation, can be difficult to resolve phylogenetically when genetic change poorly matches the rapidity of diversification. Genomic potential furnished by palaeopolyploidy, and relative roles for adaptation, random drift and hybridisation in the apportionment of genetic variation, remain poorly understood factors. Here, we study these aspects in a model radiation, Syzygium, the most species-rich tree genus worldwide. Genomes of 182 distinct species and 58 unidentified taxa are compared against a chromosome-level reference genome of the sea apple, Syzygium grande. We show that while Syzygium shares an ancient genome doubling event with other Myrtales, little evidence exists for recent polyploidy events. Phylogenomics confirms that Syzygium originated in Australia-New Guinea and diversified in multiple migrations, eastward to the Pacific and westward to India and Africa, in bursts of speciation visible as poorly resolved branches on phylogenies. Furthermore, some sublineages demonstrate genomic clines that recapitulate cladogenetic events, suggesting that stepwise geographic speciation, a neutral process, has been important in Syzygium diversification

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Genomic insights into rapid speciation within the world's largest tree genus Syzygium

The relative importance of the mechanisms underlying species radiation remains unclear. Here, the authors combine reference genome assembly and population genetics analyses to show that neutral forces have contributed to the radiation of the most species-rich tree genus Syzygium. Species radiations, despite immense phenotypic variation, can be difficult to resolve phylogenetically when genetic change poorly matches the rapidity of diversification. Genomic potential furnished by palaeopolyploidy, and relative roles for adaptation, random drift and hybridisation in the apportionment of genetic variation, remain poorly understood factors. Here, we study these aspects in a model radiation, Syzygium, the most species-rich tree genus worldwide. Genomes of 182 distinct species and 58 unidentified taxa are compared against a chromosome-level reference genome of the sea apple, Syzygium grande. We show that while Syzygium shares an ancient genome doubling event with other Myrtales, little evidence exists for recent polyploidy events. Phylogenomics confirms that Syzygium originated in Australia-New Guinea and diversified in multiple migrations, eastward to the Pacific and westward to India and Africa, in bursts of speciation visible as poorly resolved branches on phylogenies. Furthermore, some sublineages demonstrate genomic clines that recapitulate cladogenetic events, suggesting that stepwise geographic speciation, a neutral process, has been important in Syzygium diversification.Peer reviewe

Genomic insights into rapid speciation within the world's largest tree genus Syzygium

Acknowledgements Y.W.L. was supported by a postgraduate scholarship research grant from the Ministry of National Development, Singapore awarded through the National Parks Board, Singapore (NParks; NParks’ Garden City Fund). Principal research funding from NParks and the School of Biological Sciences (SBS), Nanyang Technological University (NTU), Singapore, is acknowledged. We thank Peter Preiser, Associate Vice President for Biomedical and Life Sciences, for facilitating NTU support, and Kenneth Er, CEO of NParks, for facilitating research funding through that organisation. V.A.A. and C.L. were funded by SBS, NTU for a one-year research leave. V.A.A. and C.L. also acknowledge support from the United States National Science Foundation (grants 2030871 and 1854550, respectively). S.R. was supported by a postdoctoral research fellowship under the NTU Strategic Plant Programme. S.R. and N.R.W.C. acknowledge funding from NTU start-up and the Academy of Finland (decisions 318288, 319947) grants to J.S. Fieldwork conducted by Y.W.L. was supported by an Indonesian Government RISTEK research permit (Application ID: 1517217008) and an Access License from the Sabah State government [JKM/MBS.1000-2/2JLD.7(84)]. T.N.C.V. is grateful to the Assemblée de la Province Nord and Assemblée de la Province Sud (New Caledonia) for facilitating relevant collection permits. A.N. was partly supported by the Research Project Promotion Grant (Strategic Research Grant No. 17SP01302) from the University of the Ryukyus, and partly by the Environment Research and Technology Development Fund (JPMEERF20204003) from the Environmental Restoration and Conservation Agency of Japan. Fieldwork in Fiji conducted by R.B. was hosted and facilitated by Elina Nabubuniyaka-Young (The Pacific Community’s Centre for Pacific Crops and Trees, Fiji). We thank the NTU-Smithsonian Partnership for tree data obtained for the Bukit Timah Nature Reserve (BTNR) long-term forest dynamics plots. Administrative support provided by Mui Hwang Khoo-Woon and Peter Ang at the molecular laboratory of the Singapore Botanic Gardens (SBG) is acknowledged. Rosie Woods and Imalka Kahandawala (DNA and Tissue Bank, Royal Botanic Gardens, Kew) facilitated additional DNA samples. Daniel Thomas (SBG) and Yan Yu (Sichuan University) commented on biogeographical analyses. NovogeneAIT in Singapore is acknowledged for personalised sequencing service.Peer reviewedPublisher PD