The F1 chaperone:usher translocon of Yersinia pestis and potential applications

Plague is a notifiable disease caused by Yersinia pestis for which there is still no reliable vaccine available. The fraction 1 (F1) antigen forms an immunogenic capsule around the cell surface that decreases efficiency of phagocytosis. Many E. coli strains and other Gramnegative bacteria coat themselves in similar, remarkably stable protein fibres assembled via specific, dedicated chaperone-usher (CU) pathways. Fibres are assembled through a pore within each usher protein, via a cycling of specific chaperone:subunit:usher interactions leading to subunit polymerisation and translocation to the cell surface. This project has used bioinformatics analysis and modelling to improve understanding of details of the Y. pestis F1 chaperone:usher translocon and has applied this knowledge to enhance export of heterologous epitopes. The number of members of the γ3 family of ushers, which assemble simple fibres of one or two subunits, has been expanded and includes for the first time a CU system more closely related to that of the Yersinia Caf system. This plasmid encoded usher from the commensal E. coli SE11 shares 70% identity with Caf1A. Caf1A usher was modelled using Intfold and ITASSER, based on the crystal structures of E. coli FimD and PapC usher in the closed state (PDB: 2VQI, 3.2Å). The complete Caf translocon was modelled based on the open FimD structure (PDB: 3RFZ, 2.8Å) with the Caf1M chaperone:Caf1:Caf1 subunit structure (PDB:1Z9S, 2.2Å) docked in the translocon. Based on the modelled Caf translocon and multiple sequence alignments of related ushers, conserved residues within the β-barrel facing the pore cavity or subunit; residues interacting between the plug and β-barrel in the closed pore and residues interacting between β-barrel and subunit in the ‘open’ translocating pores were identified. These were then tested by mutagenesis for impact on F1 assembly. No single point mutation within the usher abolished F1 assembly. The most profound effect was following mutation of Ser289 to Ala, the level of surface F1 decreased to 70.81% ± 3.0 of levels with wildtype Caf1A. The potential of F1 fibre to act as a carrier of epitopes was tested by replacing 4 loops within Caf1 with either Gly residues or charged residues. The model was used to understand and optimise limitations in export of modified fibres. One permissive site (loop 5) was identified as the optimum site for loop replacement and surface assembly of modified F1 was enhanced by mutation of a clashing Gln in the β-barrel wall. In addition, the study identified a critical role for a conserved Asn, Asn80, within loop 2 of Caf1 subunit that was modelled interacting with Tyr266 in the plug. The permissive loop 5 was also adapted to export a polyhistidine sequence. While 4 His residues were readily accommodated, F1::1His6 conferred toxicity, although there was still evidence of surface polymer. Thus, this study demonstrated flexibility of the F1 CU pathway for surface display of short peptides and the ability to use the translocon model to identify problem areas and repair export. As F1 is considered to be unique to Y. pestis, the presence of a Caf related CU locus in a commensal E. coli was of interest to understanding its phylogenetic relationship to F1 and also in diagnostic applications in plague detection. Bioinformatic analysis and recombinant expression of the E. coli SE11-P2 CU locus, combined with mass spectrometry analysis, confirmed surface assembly of polymers of both subunits from this locus. A purification strategy for isolation of recombinant SE11-P2 polymers was developed. Purified protein will be used in future studies to raise antibody for further study of this CU system and to test for any cross-reaction with Y. pestis F1 antigen, that might potentially interfere with serological tests for Y. pestis. F1 antigen remains a component of interest in both anti-plague vaccine design and plague detection. Results from this study have potential to improve reliability of both approaches to plague control

The effect of fasting during Ramadan towards improvement of type 2 Diabetes mellitus

Introduction: Globally, the number of people with diabetes has been increasing trend in this modern day. Thus, this study aimed to explain the main factors of Type 2 Diabetes Mellitus (T2DM), to compare the random or fasting blood sugar before, during and after fasting month (Ramadan), and to determine the association between fasting and improvement of T2DM. Method: The total respondents of this study were 58 patients from Medical Outpatient Department. This study was used retrospective cohort study design. The data collected and recorded based on the inclusion and exclusion criteria. The fasting blood sugar for before, during and after the month of Ramadan was recorded in the designed form. The data were analysed by using SPSS version 20. Results: There were three factors of T2DM, obesity, smoking, and family history. There was no significant change of fasting blood glucose result for the comparison of three periods of time except one pair with p value of less than 0.05. There were no significant for the association between fasting and improvement of T2DM. In this study, researcher states that <0.05 was significant pvalue. Conclusion: This study concluded that there was no association between fasting and T2DM. This might be related to many factors such as the behaviour and disciplined of people in desire of consuming food and limited data collection

The impact of electronic gadget uses with academic performance among secondary school students

Introduction: Many school students who own electronic gadget spent most of their time on it. As a result, both of the aspect of academic achievement and health status is affected as they are too dependent on electronic gadget. Objective: The general objective of this study was to determine the association of electronic gadget use with academic performance and health status among selected secondary school students in Kuantan, Pahang. Materials and Methods: A descriptive, cross sectional study by using convenient sampling was conducted on sample size of 233 school students at three selected secondary schools involving SMK Pelindung, SMK Bukit Goh and SMK Teluk Chempedak. The instrument used was structured questionnaire to assess the total time spent on electronic gadget, students’ academic performance and students’ health status. The data was analysed by using SPSS version 20 in term of descriptive statistic and Pearson Chi-Square test to test the significant association. Result: There were 233 school students who involved in this study and majority of them (59.2%) were Malay. For gender, 53.2% were male and 46.8% were female. In total of 48.1% students were spending time more than 6 hours on electronic gadget and the remaining 51.9% students spending time less than 5.99 hours on electronic gadget. Based on the findings, the result showed that there were significant association between race, gender, parent income, level of dependency, academic performance and health status and the total time spent on electronic gadget but opposing, there were no significant association between years started using electronic gadget and total time spent on electronic gadget. Conclusion: Majority of students who spent more time on electronic gadget use has high level of dependency towards gadget, poor academic achievement and good health status. Thus, the healthcare providers should plan effective intervention such as introduce application on electronic gadget for academic purposes and health tracking to overcome these problems so that students can balance between their academic achievement and health status and increase wellness and health among school students

The influence of parenting styles on parental political orientation and voting behavior of young adult

The main purposes of the study are to examine the relationship between parenting styles and parental political orientation and to find out whether voting behavior of young adults is associated with parenting practices. 39 items on parenting styles, parental political orientation & voting behavior were completed by 239 respondents. The data was collected using a structured questionnaire. Approximately, 300 sets of questionnaires were distributed among students and approximately 239 questionnaires were collected back and returned from respondents progressively. This study used descriptive, factor analysis, and cluster analysis. Furthermore, the data was also verified using Mann-Whitney and multiple regression analysis to test predictability of independent variables. The results show that there are four parenting practices among parents of IIUM students which are consistent with Baumrind’s authoritarian, authoritative, permissive and neglectful typologies. In addition, the study indicates that authoritarian parents have proactive involvement in knowledge transmission of politics to their offspring. On the other hand, surprisingly in the latter test reveals that high representation of young adults in election is positively associated with authoritative parenting. Despite the fact that authoritarian parents are identified as the active agent in political socialization, authoritative parents however, scored positive behavior to young adults’ attitudes in voting. Evaluating the issues of falling level of electoral participation among young adults, this research looks into the possible reasons that contribute to young adult’s turning out and not turning out for election. Keywords: Political Orientation, 4 Parenting Styles; Authoritarian, Authoritative and Neglectful, Permissive and Voting Behavio

Knowledge and awareness on computer vision syndrome (CVS) and their contributing factor among undergraduate university students

The surge in the use of digitization in daily life has led to a condition known as computer vision syndrome (CVS), which is at risk of becoming a major health issue involving the vision and musculoskeletal systems. Thus, this study will determine the level of knowledge and awareness of CVS among International Islamic University Malaysia (IIUM) Kuantan students. A quantitative cross-sectional study with convenience sampling was conducted among 216 undergraduate students at the IIUM Kuantan Campus from October to November 2021. Around 79.2% of respondents never heard of the term CVS. The majority of the respondents use mobile phones (52.3%) compared to other digital devices and spend more than 3 hours in front of the screen per day (48.6%). In addition, most of them experience neck, back, or shoulder pain (77.8%), fatigue (65.3%), headaches (64.4%), and eyestrain (74.1%). The respondents also complained of joint pain in the fingers and wrists (52.3%) and shoulder pain (60.6%). The majority of the respondents had a high level of knowledge regarding CVS (94.9%) but had a moderate level of awareness regarding CVS (65.7%). As current education and lifestyle are more interrelated to digital device usage, it is recommended that more educational and awareness programmes on CVS be promoted

Synbiotic Musa acuminata skin extract and Streptococcus salivarius K12 inhibit candida species biofilm formation

This study aimed to determine the effect of synbiotic Musa acuminata skin extract (MASE) and Streptococcus salivarius K12 (K12) on Candida species biofilm formation. Liquid chromatography quadrupole time-of-flight (LC-Q-TOF-MS) was conducted to characterize MASE. To determine the effect of synbiotic on Candida biofilm, 200 mL of RPMI-1640 containing Candida, K12, and MASE were pipetted into the same well and incubated at 37�C for 72h. A similar protocol was repeated with K12 or MASE to determine the probiotic and prebiotic effects, respectively. Dimorphism, biofilm biomass, and Candida total cell count (TCC) were determined. A total of 60 compounds were detected in MASE. C. albicans (ALT5) and Candida lusitaniae exhibited the highest reduction in biofilm biomass when co-cultured with prebiotic (77.70 ± 7.67%) and synbi- otic (97.73 ± 0.28%), respectively. All Candida spp. had decreased TCC and hyphae when co-cul- tured with synbiotic. In conclusion, MASE and K12 inhibit Candida biofilm formation

Anti-cancer activities of β-mangostin against oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of malignant tumors with poor prognosis resulting in major morbidity and mortality. The actual curative treatment is usually chemotherapy with concurrent radiation, sometimes combined with surgery. Unfortunately, the strength of the drugs used in chemotherapy causes side effects that can bring discomfort and inconvenience. Herbal remedies have been used for thousands of years with very minimal side effects and clearly merit extended research for their ability to selectively kill cancer cells. The genus of Garcinia is well known as a medicinal plant in Southeast Asia. β-mangostin, a xanthone from the pericarps of various species of Garcinia has been shown to exhibit anti-cancer activities in various human cancer cells. However, no attempt has been made to explore the potential benefits of this xantone for treatment and/or prevention of OSCC. Here, we report that β- mangostin exhibits anti-proliferative effect and induces apoptosis in human oral squamous cell carcinoma cell lines HSC-3 and Ca-922. MTT assay showed that β-mangostin markedly inhibited proliferation of HSC-3 and Ca-922 cells in a dose- and time-dependent manner. The apoptosis induced by β-mangostin was clearly detected by flow cytometry in both cell lines and confirmed by caspase activity assays. Moreover, quantitative RT-PCR revealed that apoptotic activity by β-mangostin in HSC-3 and Ca-922 cells is associated with an up-regulation of caspase - 8 and pro-apoptotic PUMA genes. These results identify β-mangostin as a potential therapeutic agent for human oral squamous cell carcinoma

Knowledge, attitude and practice on sexual health among students of Centre for Foundation Studies

Introduction: Sexual health is not merely just avoiding infectious disease or unwanted pregnancy, but it is broader issue that required serious attention. People with sexually transmitted infection or unwanted pregnancy also have the chances to be sexually healthy. In order to be sexually healthy, ones must recognize the sexual rights that we share, having the access to get the sexual health education, and able to communicate with the healthcare providers regarding the issues of sexual health and empowered to prevent sexually transmitted disease and unwanted pregnancy. Aims: This study aims to determine the level of knowledge, attitudes, and practices on sexual health among the students of centre for foundation studies (CFS). Method: A cross-sectional study was conducted among 320 participants by using a close-ended question. Result: The results showed that, there were high level of knowledge on sexual health among CFS students with excellent understandings on non-permissible premarital sexual intercourse displayed by their non-experience confessions. Conclusion: This study findings can be used for future to develop intervention in order to decrease the sexual health problems by enlightening the students on proper knowledge, attitude and practice on sexual health

Knowledge, attitude and awareness of basic life support among health sciences university students

Objective: Basic life support (BLS) refers to the skills that require no or few equipment to save cardiac or respiratory arrest patients and it is a skill that required by all healthcare providers including medical-based students in order to save the life-threatening victims. This study determined the level of knowledge, attitude and awareness of BLS among students at International Islamic University Malaysia (IIUM) Kuantan campus. Methods: A quantitative cross-sectional study with convenience sampling study was conducted among 167 students at IIUM Kuantan Campus, from November to December 2020. Data were gathered by using Google Forms which available in English Language and distributed to year 3, 4 and 5 students. The questionnaire was adapted from three sets questionnaires, which two sets questionnaires were from American Heart Association in 2015, and another set questionnaire from European Resuscitation Council (ERC) 2010 Resuscitation Guidelines. Results: The majority of the respondents have high awareness and positive attitude towards BLS but having below average score for knowledge on BLS. There is a significantly association between courses and previous exposure of BLS training with BLS knowledge (p<0.05). Age, courses and previous exposure of BLS training are significantly associated with awareness level of BLS (p<0.05). A significant association also observed between previous exposure of BLS training with positive attitude towards BLS training (p<0.05). Conclusion: Health sciences university students was concluded to having positive attitude and high awareness towards BLS training despite having below average level of BLS knowledge score. Therefore, the university may provide more BLS educational programs and even practical to the students to promote their knowledge and improve their skills on BLS

Genome comparison of Actinomyces naeslundii with 25 known probiotics

Introduction: Actinomyces naeslundii is an oral microbiome that has been suggested to involve in actinomycosis particularly in immunocompromised patients. However, studies have also shown that the bacterium can inhibit the colonisation of Candida albicans and cariogenic bacterium, Streptococcus mutans. Even though various studies have been conducted to characterise A. naeslundii, however, the role of the bacterium in the oral cavity either to induce pathogenicity or to improve oral health remain unclear. The objective of this study is to determine the role of A. naeslundii in the oral cavity using bioinformatic tools with the hypothesis that A. naeslundii possesses genome similarity to oral probiotics. Materials and method: The study was conducted by data mining of the genomic sequences of A. naeslundii NCTC10301 from GenBank. Following that, genomic comparison was performed with 25 species of well-known probiotics. MAUVE version 2.3.1 was used to find similarities between A. naeslundii with the known probiotics through identification of potential relevance probiotic properties in A. naeslundii. Phylogenetic tree was constructed using PHYLIP package to identify evolutionary relationship of A. naeslundii with the known probiotics. The 16s rRNA sequences of A. naeslundii and known probiotics were harvested from GenBank using BLAST. Finally, the functions of all A. naeslundii genes that shared similarity with known probiotics were identified using INTERPRO. Result: Genome comparison analysis of the present study showed that A. naeslundii genome exhibited high similarity to Bifidobacterium species such as B. animalis subsp. lactis, B. bifidum, B. longum and B. breve. In addition, phylogenetic tree analysis showed that Bacillus species, B. subtilis and B. cereus , appeared to clade together with A. naeslundii , with bootstrap value of 98%. Conclusion: A. naeslundii had high similarity with probiotic Bifidobacterium species thus supported the hypothesis of the present study that A. naeslundii possesses genome similarity to oral probiotic