Making connections between novel transcription factors and their DNA motifs

The key components of a transcriptional regulatory network are the connections between trans-acting transcription factors and cis-acting DNA-binding sites. In spite of several decades of intense research, only a fraction of the estimated ∼300 transcription factors in Escherichia coli have been linked to some of their binding sites in the genome. In this paper, we present a computational method to connect novel transcription factors and DNA motifs in E. coli. Our method uses three types of mutually independent information, two of which are gleaned by comparative analysis of multiple genomes and the third one derived from similarities of transcription-factor-DNA-binding-site interactions. The different types of information are combined to calculate the probability of a given transcription-factor-DNA-motif pair being a true pair. Tested on a study set of transcription factors and their DNA motifs, our method has a prediction accuracy of 59% for the top predictions and 85% for the top three predictions. When applied to 99 novel transcription factors and 70 novel DNA motifs, our method predicted 64 transcription-factor-DNA-motif pairs. Supporting evidence for some of the predicted pairs is presented. Functional annotations are made for 23 novel transcription factors based on the predicted transcription-factor-DNA-motif connections

The impact of Asian financial crisis and global ICT sectors correction on the relationships between stock prices and exchange rates in ASEAN-5

This paper has investigated the dynamic impacts of the Asian financial crisis and global Information, Communication and Technology (ICT) sector correction on the relationships between exchange rates and stock prices for the ASEAN-5 funding countries. They are Malaysia, Singapore, Thailand, the Philippines, and Indonesia. Using daily data 1995 – 2001, the results of variance decompositions analysis suggest that during pre-crisis, crisis and ICT bubble, the exchange rates have more influential power in influencing stock prices. Thus, this finding is in line with the traditional approach of stock prices determination, where exchange rate change is expected to give rise to stock price change. However, during post-bubble period stock prices become the dominant explanatory variable in all countries

Understanding finite size effects in quasi-long-range orders for exactly solvable chain models

In this paper, we investigate how much of the numerical artefacts introduced by finite system size and choice of boundary conditions can be removed by finite size scaling, for strongly-correlated systems with quasi-long-range order. Starting from the exact ground-state wave functions of hardcore bosons and spinless fermions with infinite nearest-neighbor repulsion on finite periodic chains and finite open chains, we compute the two-point, density-density, and pair-pair correlation functions, and fit these to various asymptotic power laws. Comparing the finite-periodic-chain and finite-openchain correlations with their infinite-chain counterparts, we find reasonable agreement among them for the power-law amplitudes and exponents, but poor agreement for the phase shifts. More importantly, for chain lengths on the order of 100, we find our finite-open-chain calculation overestimates some infinite-chain exponents (as did a recent density-matrix renormalization-group (DMRG) calculation on finite smooth chains), whereas our finite-periodic-chain calculation underestimates these exponents. We attribute this systematic difference to the different choice of boundary conditions. Eventually, both finite-chain exponents approach the infinite-chain limit: by a chain length of 1000 for periodic chains, and > 2000 for open chains. There is, howwever, a misleading apparent finite size scaling convergence at shorter chain lengths, for both our finite-chain exponents, as well as the finite-smooth-chain exponents. Implications of this observation are discussed.Comment: 14 pages, 15 figure

INSECTICIDE SUSCEPTIBILITY STATUS OF FIELD- COLLECTED AEDES (STEGOMYIA) AEGYPTI (L.) AT A DENGUE ENDEMIC SITE IN SHAH ALAM, SELANGOR, MALAYSIA

Abstract. Biweekly ovitrap surveillance (OS) was conducted for a year (August 2007 -September 2008 at two different dengue endemic sites in Shah Alam, Selangor, Malaysia, 50 km from Kuala Lumpur. Aedes aegypti collected from these 2 locations were raised to the F3 stage and subjected to a WHO standard bioassay method to determine lethal time (LT) against pyrethroids (permethrin 0.75%, cyfluthrin 0.15%), organophosphates (malathion 5.0%, fenitrothion 1.0%), carbamates (propoxur 0.1%, bendiocarb 0.1%) and organochlorine (DDT 4.0%). Insecticide susceptibilities were analyzed for one year. Aedes aegypti were resistant to DDT with a mortality range of 0 -13.3% throughout the year at both sites. Susceptibilities to pyrethroids and carbamates varied throughout the year. In contrast, susceptibilities to pyrethroids and carbamates varied throughout the year: resistant to propoxur, bendiocarb and permethrin with mortality of < 80% in most months; but, showed incipient resistant to cyfluthrin in most months. Mosquitoes were consistently susceptible to malathion and fenitrothion, with complete mortality during most months. They were especially susceptible to malathion with LT 50 values of 21.32 -36.37 minutes, suggesting effectiveness of malathion for control of dengue

Using Expanded Natural Killer Cells as Therapy for Invasive Aspergillosis

Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in A. fumigatus killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against A. fumigatus conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients

Review on the Cytotoxic and Antimicrobial Properties of Xanthones from Cratoxylum cochinchinense

Cratoxylum cochinchinense is a perennial plant found in Southeast Asia, having diverse terminologies in various Southeast Asian countries. It has been traditionally used as medicine, tea and food spice. Phytochemical analysis reveals a rich array of bioactive compounds in different parts of the plant such as xanthones, caged xanthones, flavonoids, tocotrienols, triterpenoids, benzophenones and anthraquinones, which obviously possess beneficial biological properties. Among these, xanthones are the most abundant secondary metabolites in C. cochinchinense. This review presents the cytotoxic properties of xanthones present in C. cochinchinense as well as their antimalarial and antibacterial properties, further supporting the medicinal use of this plant

XBP1, Downstream of Blimp-1, Expands the Secretory Apparatus and Other Organelles, and Increases Protein Synthesis in Plasma Cell Differentiation

AbstractThe differentiation of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, Blimp-1 and XBP1. By gene expression profiling, we defined a set of genes whose induction during mouse plasmacytic differentiation is dependent on Blimp-1 and/or XBP1. Blimp-1-deficient B cells failed to upregulate most plasma cell-specific genes, including xbp1. Differentiating xbp1-deficient B cells induced Blimp-1 normally but failed to upregulate genes encoding many secretory pathway components. Conversely, ectopic expression of XBP1 induced a wide spectrum of secretory pathway genes and physically expanded the endoplasmic reticulum. In addition, XBP1 increased cell size, lysosome content, mitochondrial mass and function, ribosome numbers, and total protein synthesis. Thus, XBP1 coordinates diverse changes in cellular structure and function resulting in the characteristic phenotype of professional secretory cells

Prevalence of coronavirus disease 2019 (COVID-19) in different clinical stages before the national COVID-19 vaccination programme in Malaysia: A systematic review and meta-analysis

More than 1.75 million COVID-19 infections and 16 thousand associated deaths have been reported in Malaysia. A meta-analysis on the prevalence of COVID-19 in different clinical stages before the National COVID-19 Vaccination Program in Malaysia is still lacking. To address this, the disease severity of a total of 215 admitted COVID-19 patients was initially recorded in the early phase of this study, and the data were later pooled into a meta-analysis with the aim of providing insight into the prevalence of COVID-19 in 5 different clinical stages during the outset of the COVID-19 pandemic in Malaysia. We have conducted a systematic literature search using PubMed, Web of Science, Scopus, ScienceDirect, and two preprint databases (bioRxiv and medRxiv) for relevant studies with specified inclusion and exclusion criteria. The quality assessment for the included studies was performed using the Newcastle–Ottawa Scale. The heterogeneity was examined with an I2 index and a Q-test. Funnel plots and Egger’s tests were performed to determine publication bias in this meta-analysis. Overall, 5 studies with 6375 patients were included, and the pooled prevalence rates in this meta-analysis were calculated using a random-effect model. The highest prevalence of COVID-19 in Malaysia was observed in Stage 2 cases (32.0%), followed by Stage 1 (27.8%), Stage 3 (17.1%), Stage 4 (7.6%), and Stage 5 (3.4%). About two-thirds of the number of cases have at least one morbidity, with the highest percentage of hypertension (66.7%), obesity (55.5%), or diabetes mellitus (33.3%) in Stage 5 patients. In conclusion, this meta-analysis suggested a high prevalence of COVID-19 occurred in Stage 2. The prevalence rate in Stage 5 appeared to be the lowest among COVID-19 patients before implementing the vaccination program in Malaysia. These meta-analysis data are critically useful for designing screening and vaccination programs and improving disease management in the country

Australasian Malignant PLeural Effusion (AMPLE)-3 trial: Study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion

Introduction: Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. Methods and analysis: A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. Ethics and dissemination: Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. Discussion: Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. Trial registration: Australia New Zealand Clinical Trial Registry ACTRN12618001013257. Registered on 18 June 2018. Protocol version: Version 3.00/4.02.1

Methodology of National Health and Morbidity Survey (NHMS): adolescent health, Malaysia 2022

In Malaysia, the adolescent health surveys conducted in 2012 and 2017 revealed an increasing trend of adolescent health risk behaviours and protective factors. This current article aims to describe the methodology of the National Health and Morbidity Survey (NHMS) 2022: Adolescent Health in Malaysia. The current nationwide cross-sectional survey of Malaysian secondary school students used multistage stratified sampling to select 240 nationally representative schools. This survey is conducted from June to July 2022 among the students in forms 1, 2, 3, 4, and 5 in all Malaysian states by 34 data collection teams. A validated self-administered questionnaire is used, similar to those used in the NHMS 2012 and NHMS 2017. The quality control is done twice, once at the field level and once at the central level. Sample weighting and analysis are conducted using SPSS statistical software version 28.0. A total of 239 out of 240 randomly selected schools with 33,523 adolescents are involved in this study (overall response rate is 89.0%). The distribution of state, sex, and form among adolescents is almost equal. Compared to both previous adolescent health surveys using the same methodology and approaches, the overall response rates for NHMS 2017 and NHMS 2012 are 89.2% and 88.8%, respectively. The implementation of NHMS 2022 has employed an acceptable methodology for a survey of the adolescent population. This reliable data provides national estimates for adolescent health risk behaviours and protective factors. The survey allows the relevant authorities to carried out further improve the health status of adolescents in Malaysia